A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ATI-450 vs Placebo in Patients With Moderate to Severe Hidradenitis Suppurativa (HS)
Phase: PHASE2
Conditions: Hidradenitis Suppurativa
Sponsor: Aclaris Therapeutics, Inc.

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Protocol ATI-450-HS-201 - Version 5.0 
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TITLE PAGE 
Protocol Title: A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Investigate the 
Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ATI-450 vs Placebo in 
Patients with Moderate to Severe Hidradenitis Suppurativa (HS)  
Protocol Number: ATI-450-HS-201 
Version Number: 5.0 
Product: ATI-450 
Short Title: ATI-450 vs Placebo in Patients with Moderate to Severe Hidradenitis Suppurativa (HS) 
Study Phase: 2a 
Sponsor Name: Aclaris Therapeutics, Inc 
Legal Registered Address:  
640 Lee Rd, Ste 200 
Wayne, PA 19087, US 
Regulatory Agency Identifying Number(s): IND No. 157784 
Date of Protocol: 04 August 2022 (Amendment 4, Version 5.0) 
NCT #: NCT05216224

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Protocol ATI-450-HS-201 - Version 5.0 
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Sponsor Signatory 
This study will be conducted in compliance with the clinical study protocol (and amendments), 
International Council for Harmonisation (ICH) guidelines for current Good Clinical Practice (GCP) and 
applicable regulatory requirements. I have read this protocol in its entirety and agree to conduct the study 
accordingly: 
Aclaris Therapeutics, Inc 
 
Date 
Medical Monitor name and contact information can be found in Appendix 2. 
 
8/4/2022

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Protocol ATI-450-HS-201 - Version 5.0 
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TABLE OF CONTENTS 
 
TABLE OF TABLES ...............................................................................................................9 
TABLE OF FIGURES ...........................................................................................................10 
1.0 
PROTOCOL SUMMARY ........................................................................................11 
1.1 
Synopsis ...........................................................................................................11 
1.2 
Schema ............................................................................................................19 
1.3 
Schedule of Assessments ................................................................................20 
2.0 
INTRODUCTION......................................................................................................24 
2.1 
Study Rationale ..............................................................................................24 
2.2 
Background ....................................................................................................24 
2.3 
 
3.0 
OBJECTIVES AND ENDPOINTS ..........................................................................28 
4.0 
STUDY DESIGN ........................................................................................................30 
4.1 
Overall Design ................................................................................................30 
4.2 
Scientific Rationale for Study Design ...........................................................30 
4.3 
 
4.4 
End of Study Definition .................................................................................31 
5.0 
STUDY POPULATION ............................................................................................32 
5.1 
Inclusion Criteria ...........................................................................................32 
5.2 
Exclusion Criteria ..........................................................................................33 
5.3 
Lifestyle Considerations ................................................................................36 
5.4 
Screen Failures ...............................................................................................36 
5.4.1 
Retesting During Screening ...............................................................36 
5.4.2 
Rescreening .......................................................................................36 
5.5 
COVID-19 Guidance .....................................................................................36 
5.5.1 
COVID-19 Vaccination and Treatment Guidance ............................36 
5.5.2 
COVID-19 Testing Guidance ............................................................37 
6.0 
STUDY TREATMENT .............................................................................................39 
6.1 
Study Treatment(s) Administered ................................................................39 
6.2 
Preparation/Handling/Storage/Accountability ...........................................39 
6.3 
Measures to Minimize Bias: Randomization and Blinding........................40 
6.4 
Study Treatment Compliance .......................................................................40 
6.5 
Concomitant Therapy ....................................................................................41 

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6.5.1 
Rescue Medicine ...............................................................................42 
6.6 
Dose Modification ..........................................................................................42 
6.7 
Treatment after the End of the Study ..........................................................42 
7.0 
DISCONTINUATION OF STUDY TREATMENT AND PATIENT 
DISCONTINUATION/WITHDRAWAL ................................................................43 
7.1 
Discontinuation of Study Treatment ............................................................43 
7.1.1 
Liver Function ...................................................................................43 
7.1.2 
Neutrophil Laboratory Values ...........................................................44 
7.1.3 
Creatine Kinase Laboratory Values ...................................................44 
7.1.4 
Skin Toxicity .....................................................................................44 
7.2 
Temporary Discontinuation ..........................................................................44 
7.2.1 
Unrelated Adverse Events or COVID-19 Diagnosis .........................44 
7.2.2 
ECG Criterion for Drug Discontinuation ..........................................44 
7.3 
Rechallenge .....................................................................................................45 
7.4 
Patient Discontinuation/Withdrawal from the Study .................................45 
7.5 
Lost to Follow-up ...........................................................................................46 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ....................................................47 
8.1 
Efficacy Assessments .....................................................................................47 
8.1.1 
Lesion Counts—Abscess, Nodule and Draining Fistulas 
(tunnels) .............................................................................................47 
8.1.2 
Patient's Global Assessment of Skin Pain .........................................49 
8.1.3 
Dermatology Life Quality Index .......................................................49 
8.1.4 
Hidradenitis Suppurativa-Physician’s Global Assessment ...............50 
8.1.5 
Hurley Staging System ......................................................................51 
8.1.6 
Lesion Photography ...........................................................................51 
8.2 
Safety Assessments .........................................................................................51 
8.2.1 
Physical Examinations .......................................................................51 
8.2.2 
Vital Signs .........................................................................................52 
8.2.3 
Electrocardiograms ............................................................................52 
8.2.4 
Clinical Safety Laboratory Assessments ...........................................53 
8.3 
Adverse Events ...............................................................................................53 
8.3.1 
Time Period and Frequency for Collecting AE and SAE 
Information ........................................................................................54 
8.3.2 
Method of Detecting AEs and SAEs .................................................54 
8.3.3 
Follow-up of AEs and SAEs .............................................................54 
8.3.4 
Regulatory Reporting Requirements for SAEs .................................54 
8.3.5 
Pregnancy ..........................................................................................55 
8.3.6 
Adverse Events of Special Interest ....................................................55 
8.3.7 
Disease-related Events and/or Disease-related Outcomes Not 
Qualifying as AEs or SAEs ...............................................................56 
8.4 
Treatment of Overdose ..................................................................................56 
8.5 
Pharmacokinetics ...........................................................................................56 
8.6 
 ........................................................................................57 
8.7 
Genetics ...........................................................................................................58 

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8.8 
Biomarkers .....................................................................................................58 
8.9 
Medical Resource Utilization and Health Economics.................................58 
9.0 
STATISTICAL CONSIDERATIONS .....................................................................58 
9.1 
Statistical Hypotheses ....................................................................................58 
9.2 
Sample Size Determination ...........................................................................58 
9.3 
Populations for Analyses ...............................................................................59 
9.4 
Statistical Analyses.........................................................................................59 
9.4.1 
Efficacy Analyses ..............................................................................60 
9.4.2 
Safety Analyses .................................................................................60 
9.4.3 
Other Analyses ..................................................................................61 
9.4.4 
Missing Data ......................................................................................61 
9.5 
Interim Analyses ............................................................................................61 
9.6 
Data Monitoring Committee .........................................................................61 
10.0 
REFERENCES ...........................................................................................................62 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF TABLES 
Table 1 
Schedule of Assessments .................................................................................20 
Table 2 
Study Objectives and Endpoints ......................................................................28 
Table 3 
Study Treatment Details ..................................................................................39 
Table 4 
Analysis Sets ....................................................................................................59 
Table 5 
Efficacy Analyses ............................................................................................60 
Table 6 
Protocol-required Safety Laboratory Assessments ..........................................72 
Table 7 
Highly Effective Contraceptive Methods ........................................................84 
 

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TABLE OF FIGURES 
Figure 1 
Study Schema .................................................................................................19 
 
 

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1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Investigate the 
Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ATI-450 vs Placebo in 
Patients with Moderate to Severe Hidradenitis Suppurativa (HS).  
Short Title: ATI 450 vs Placebo in Patients with Moderate to Severe Hidradenitis Suppurativa (HS) 
Rationale:  
Hidradenitis suppurativa (HS) is a chronic inflammatory disease primarily affecting apocrine-gland-rich 
regions of the body such as the axillary and groin areas. The pathophysiology of HS is complex and has 
not been clearly defined. The primary defect in HS involves occlusion of hair follicles, which leads to 
dilatation and rupture. The resulting spillage of follicular contents into the surrounding dermis induces a 
chemotactic response from neutrophils and lymphocytes and inflammation of the hair follicle leads to 
innate and adaptive immune dysregulation. An upregulation of various cytokines, such as tumor necrosis 
factor-alpha (TNF-α), interleukin (IL)-1, IL-6, IL-8, IL-17, IL-23, and other molecules appears to be 
important in the pathophysiology of this inflammatory condition.  
The study treatment ATI-450 is an orally available, novel, potent, and selective small molecule inhibitor 
of the p38α mitogen-activated protein kinase (MAPK)/MAPK-activated protein kinase 2 (MK2) 
inflammatory signaling pathway being developed for treatment of inflammatory disorders. The p38 
MAPK pathway offers great potential in the treatment of inflammatory diseases such as hidradenitis 
suppurativa (HS). By targeting MK2, which is downstream from p38, it is believed that ATI-450 can 
effectively and safely inhibit pro-inflammatory pathways without substantially impacting other anti-
inflammatory pathways. Inhibition of MK2 by ATI-450 has been shown to reduce levels of TNF-α, ILβ, 
IL6 and IL8. Unlike monoclonal antibody approaches, ATI-450 may inhibit multiple cytokines involved 
in the pathophysiology of HS. Inhibiting multiple cytokines may deliver good efficacy. This study is 
being conducted to determine the efficacy, safety, tolerability, pharmacokinetics (PK), and 
pharmacodynamics (PD) of 12 weeks of ATI-450 exposure in patients with moderate to severe HS. This 
important data will further describe the efficacy and safety of ATI-450 in a relevant patient population. 
 
 

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Protocol ATI-450-HS-201 - Version 5.0 
 
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Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
• 
To assess the efficacy of ATI-450 in patients with 
moderate to severe HS 
• 
Change from Baseline in inflammatory 
nodule/abscess count at Week 12 
Secondary 
 
• 
To assess the efficacy and safety of ATI-450 in 
patients with moderate to severe HS 
• 
Percentage of patients achieving Hidradenitis 
Suppurativa Clinical Response (HiSCR) at 
Week 12 
 
HiSCR is defined as at least a 50% reduction from 
Baseline in the total abscess and inflammatory 
nodule (AN) count, with no increase in abscess or 
draining fistula counts. 
• 
Change from Baseline in International 
Hidradenitis Suppurativa Severity Score System 
(IHS-4) over time for the 12-week treatment 
period 
• 
Percentage of patients achieving at least a 30% 
reduction and at least 1 unit reduction from 
Baseline in the numerical rating scale (NRS30) in 
Patient's Global Assessment of Skin Pain at 
Week 12 among patients with Baseline NRS ≥3.  
 
NRS30 is evaluated based on worst skin pain in a 
24-hour recall period (maximal daily pain). 
• 
Change from Baseline in Hidradenitis 
Suppurativa-Physician Global Assessment (HS-
PGA) over time for the 12-week treatment period 
• 
Change from Baseline in Dermatology Life 
Quality Index (DLQI) over time for the 12-week 
treatment period 
 
The DLQI is a 10-item validated questionnaire 
used to assess the impact of HS disease symptoms 
and treatment on quality of life (QoL). It consists 
of 10 questions evaluating impact of skin diseases 
on different aspects of a patient's QoL over the 
prior week, including symptoms and feelings, 
daily activities, leisure, work or school, personal 
relationships, and the side effects of treatment. 
 
• 
Hurley Stage over time for the 12-week treatment 
period 
• 
Incidence of adverse events (AEs), serious AEs 
(SAEs), laboratory value abnormalities, 
electrocardiogram (ECG) abnormalities, vital 
signs abnormalities  
• 
To assess the PK of ATI-450 in patients with 
moderate to severe HS 
• 
Trough ATI450 and metabolite (CDD-2164) 
concentrations at clinic visits. On Day 1, 8, and 85 
trough and 2-hour post dose) will be collected.  

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Protocol ATI-450-HS-201 - Version 5.0 
 
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Exploratory 
 
• 
To assess the PD of ATI-450 in patients with 
moderate to severe HS 
 
 
 
 
 
 
Overall Design: 
This is a Phase 2a, randomized, double-blind, placebo-controlled study to investigate the efficacy, safety, 
tolerability, PK, and PD of ATI-450 50 mg twice daily (BID) versus placebo in patients with moderate to 
severe HS.  
• 
The study will consist of an up to 28-day Screening Period, a 12-week treatment period, and a 30-day 
follow-up period. The total duration of the study for patients remaining until their final follow-up 
assessment will be up to 21 weeks. 
• 
The Investigator will obtain signed informed consent from the patient before any study procedures are 
performed. 
• 
During the Screening Period, each patient will be required to have all assessments performed as 
outlined in the Schedule of Assessments (SoA) (Table 1).  
• 
Results for all the Screening assessments must be available at the time patient eligibility is 
reconfirmed prior to randomization and dosing. 
• 
Patients whose eligibility is confirmed at Baseline will be randomized in a 1:1 ratio to receive either 
ATI-450 tablets (50 mg BID) or matching placebo tablets BID. Study treatments will be administered 
orally for 12 weeks.  
• 
Patients will attend clinic visits on Days 1, 8, 15, 29, 43, 57, and 85 for safety, efficacy, PK, and PD 
assessments. The morning dose of study treatment will be administered in the clinic on each study 
visit day. 
• 
On Day 85 (Week 12), patients will complete the end of study (EOS) assessments. A safety follow-up 
visit will be conducted 30 days after the last dose of study treatment for patients who completed the 
treatment period, as well as those who discontinue early.  
• 
The study is randomized and double-blinded to prevent bias in treatment allocation and in the 
assessment of treatment effect. 
Number of Investigators and Study Centers: 
Approximately 20 Investigators and study centers in the United States are expected to participate in this 
study. 
Number of Patients: 
It is planned to randomize approximately 90 patients, 45 patients per arm (Section 9.2). 
Treatment Groups and Duration: 
Patients will be randomized to receive ATI-450 or placebo BID for 12 weeks; however, study duration 
will be up to 21 weeks. 
Target Population: Male or nonpregnant, nonbreastfeeding female patients between 18 and 70 years of 
age, inclusive, at the time of signing the ICF, who have been diagnosed with moderate to severe HS. 
Inclusion Criteria 
Patients must meet the following criteria to be eligible for participation in the study: 

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Protocol ATI-450-HS-201 - Version 5.0 
 
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1. Able to comprehend and be willing to sign the Institutional Review Board (IRB)-approved patient 
ICF prior to administration of any study-related procedures. 
2. Patient with HS for at least 1 year (365 days) prior to Baseline visit; duration of disease as 
determined via Investigator review of patient medical history. 
3. Patient must have stable HS for at least 60 days prior to Screening visit and at Baseline visit as 
determined via Investigator review of patient medical history. 
4. Total abscesses and/or nodule (AN) count of ≥5 at Baseline visit. Abscesses and nodules must 
have the following signs of inflammation. (Inflammatory nodules should be raised): 
a. Clinical evidence of erythema and/or warmth. 
b. Clinical evidence of pain/tenderness. 
5. HS lesions present in at least 2 distinct anatomical areas at Screening and Baseline. (Bilateral 
involvement of the same area counts as 2 areas, eg, involvement of right and left axilla.)  
6. Draining fistula count of ≤20 at Baseline visit. 
7. Male or nonpregnant, nonbreastfeeding female patients between 18 and 70 years of age, 
inclusive, at the time of signing the ICF. 
a. Heterosexually active female patients who are of childbearing potential must use 
2 methods of highly effective contraception, 1 of which must be a physical barrier, for the 
duration of the study and for 30 days after the last dose (see Appendix 6).  
b. Heterosexually active male patients of childbearing potential with a female partner of 
childbearing potential must agree to use a condom plus another highly effective form of 
birth control for the duration of the study and for 90 days after the last dose (Appendix 
6Appendix6).  
8. Female patients of childbearing potential must have a negative serum pregnancy test at Screening 
and a negative urine pregnancy test prior to dosing on Day 1. 
9. Screening laboratory evaluations (hematology, chemistry, coagulation, and urinalysis) must fall 
within the normal range of the central laboratory's reference ranges unless the results have been 
determined by the Investigator to not be clinically significant. 
10. No COVID-19 vaccination or booster within the 4 weeks prior to randomization. Note: COVID 
vaccination is highly encouraged but not required. 
Exclusion Criteria 
A patient who meets any of the following exclusion criteria will not be eligible for inclusion in the study: 
1. Patient has a history of active skin disease other than HS that could interfere with the assessment 
of HS. 
2. Patient has an uncontrolled non-immunoinflammatory disease that may place the patient at 
increased risk during the study or impact the interpretation of results, eg, previous malignancy, 
previous venous thromboembolism. 
3. History or evidence of active tuberculosis, irrespective of prior or current treatment status; or 
current or prior untreated latent tuberculosis. Note: Prior latent tuberculosis with completed 
treatment is not an exclusion. 
4. Known hypersensitivity to ATI-450. 
5. Patient is an alcoholic, or has a history of alcoholism, alcoholic liver disease, or other chronic 
liver disease. 
6. Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. 

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7. Positive for human immunodeficiency virus (HIV), hepatitis B or C. Note: Patients with hepatitis 
B surface antibody without the presence of hepatitis B surface antigen will be allowed to 
participate. Patients with hepatitis C antibody positive can have Hepatitis C viral load tested, if 
the Hepatitis C virus is undetectable and the patient has been off antivirals for 6 months, he/she 
may be enrolled in the study. 
8. Tests performed at a central laboratory at Screening that meet any of the criteria below (out of 
range labs may be rechecked once, after consultation with the Medical Monitor, before patient is 
considered a screen failure): 
a. White blood cell count <3.0×103 cells/mm3.  
b. Absolute neutrophil count <1.5×103 cells/mm3. 
c. Lymphocyte count <0.5×103 cells/mm3. 
d. Platelet count <100×103 cells/mm3. 
e. Hemoglobin <10 g/dL. 
f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥1.5 × upper limit 
of normal (ULN). 
g. Total bilirubin level >2 × ULN unless patient has been diagnosed with Gilbert syndrome 
and this is clearly documented. 
h. Estimated glomerular filtration rate (eGFR), <40 mL/min/1.73 m2 based on Modification 
of Diet and Renal Disease formula. 
9. Any clinically significant laboratory abnormality that would affect interpretation of study data or 
safety of the patient’s participation in the study, per judgment of the Investigator. 
10. Clinically significant abnormal findings other than HS from physical examination (PE) conducted 
at Screening visit (Visit 1) and at Baseline visit (Visit 2) that may affect the interpretation of 
study data or the safety of the patient’s participation in the study, per the judgment of the 
Investigator. 
11. Clinically important history of a medical disorder that would compromise patient safety or data 
quality, per judgment of the Investigator. 
12. Blood pressure levels (in semi-supine position after at least 5 minutes rest): <90 mmHg or 
>150 mmHg for systolic blood pressure (BP) or <40 mmHg or >90 mmHg for diastolic BP. 
13. Patient has experience with >2 biologics, >1 Janus kinase (JAK) inhibitor, or a combination of 
1 biologic experience and 1 JAK inhibitor. 
 
 
 
 
 
 
 
 

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15. Are currently receiving corticosteroids at doses greater than 10 mg per day of prednisone (or 
equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks 
of the Screening visit. 
16. Have been using prescription topical therapies for treatment of HS within 14 days prior to 
Baseline visit. 
17. Oral or topical tetracycline class antibiotics for treatment of HS are allowable if patient is on a 
stable dose for 4 weeks prior to Baseline and willing and able to maintain the stable dose for 
duration of study. 
 
 
 
 
20. Patients with history of stroke. 
21. Significant active cardiac disease, in the past 6 months, that would affect interpretation of study 
data or the safety of the patient’s participation in the study, per judgment of the Investigator. This 
includes myocardial infarction or unstable angina, acute coronary syndrome, or heart failure with 
New York Heart Association Class II, III or IV symptoms. In addition, patients with a personal or 
family history of congenital long QT syndrome, Torsades de Pointes, sustained or symptomatic 
VT, or unexpected sudden cardiac death. 
22. Patients with any of the following Baseline predose ECG findings: 
a. Mean QTcF >450 msec as averaged on triplicate ECG; 
b. ECG or historical evidence of Wolff-Parkinson-White Syndrome (unless ablated); 
c. If atrial fibrillation or flutter is present, the mean ventricular response must be < 90 BPM 
and the patient must be anticoagulated according to national guidelines; and/or 
d. Any other finding that is considered clinically significant. 
23. Any dermatologic surgery or procedure in the past 90 days prior to Screening. 
24. Known exposure to an individual with a confirmed, active diagnosis of COVID-19 at any time 
during the Screening Period. 
25. Participated in another ATI-450 clinical study. 
26. History of clinically significant drug abuse within 2 years prior to Screening. Note: Marijuana use 
is allowed if not considered substance abuse by the investigator. 

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27. Uncontrolled hypokalemia (<3.8mmol/L), or uncontrolled hypomagnesemia (< LLN). 
 
 
 
 
 
 
 
 
Statistical methods: 
Details of all statistical summaries will be provided in the study-specific statistical analysis plan (SAP). 
All data will be presented by treatment group. Descriptive statistics (number of observations, mean, 
standard deviation, median, minimum, and maximum) will be provided for continuous variables, and 
counts and percentages will be presented for categorical variables. Unless otherwise stated, hypothesis 
tests and corresponding P values will be 1-sided with an alpha level of 0.05. No adjustments will be made 
for multiplicity. 
Baseline is defined as the last nonmissing measurement before, or on the date of first administration of, 
study treatment. 
Determination of Sample Size 
Ninety (90) randomized patients will provide 90.3% power to demonstrate the superiority of ATI-450 to 
placebo in the reduction in inflammatory nodules and abscesses at Week 12. This power computation 
assumes that the reduction in the placebo arm will be on average 2.5 nodules/abscesses and the ATI-450 
reduction will be on average 4.75 nodules/abscesses. The assumed standard deviation for the number of 
nodules/abscesses was assumed to be 3.6. These sample size assumptions were based on the values 
observed in the adalimumab PIONEER I and PIONEER II Phase 3 trials (Frew et al, 2020).  The assumed 
reduction in nodules/abscesses for ATI-450 was chosen to be slightly less than that shown in the 
PIONEER I and PIONEER II Phase 3 to account for the potential impact of dropouts on the efficacy. 
Interim Analyses 
No interim analysis is planned. 
Analysis Populations 
• 
The Full Analysis Set (FAS) population will include all patients who have been randomized and 
administered at least 1 dose of study treatment. The efficacy analyses will be conducted on the 
FAS population as randomized. 
• 
The Per Protocol (PP) population will include all randomized patients who remain on study 
treatment, complete assessments for their Day 85 visit, and do not have any major protocol 
violations. 
• 
The Safety Analysis Set population will include all patients who: are randomly assigned to study 
treatment, and take at least 1 dose of study treatment. Patients will be analyzed according to the 
treatment they actually received. 

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• 
The PK population will include all patients randomly assigned to study treatment and who take at 
least 1 dose of study treatment and have at least 1 evaluable PK measurement. 
• 
The PD population will include all patients randomly assigned to study treatment and who take at 
least 1 dose of study treatment and have at least 1 evaluable PD measurement. 
Efficacy Analyses 
All efficacy summaries will be conducted on both the FAS and PP populations.  
The primary efficacy analysis will be the treatment comparison of the change from Baseline in 
inflammatory nodules and abscesses at Week 12 in the FAS population. This analysis will be conducted 
within the context of a Mixed Model Repeated Measures (MMRM). This model will include factors for 
treatment group, time, and time by treatment interaction as well as a Baseline covariate. Patient identifiers 
will be included in the model in a manner that allows observations within a given patient over time to be 
treated as repeated measures. Point estimates and 90% confidence intervals (CIs) for the difference in 
least square means (LS means) will be provided in addition to the 1-sided P values.  
Treatment comparisons for all secondary responder endpoints (percentage of patients meeting HiSCR at 
Week 12, percentage of patients achieving at least 30% reduction from Baseline in NRS30 in PGA Skin 
Pain, and percentage of patients who experience at least a 25% increase in AN count with a minimum 
increase of 2 relative to Baseline over the 12-week treatment period) will be conducted using a logistic 
regression applied to each time point separately. The logistic regression will include a factor for treatment 
group and a covariate for Baseline, where appropriate. These analyses will be done for both the FAS and 
PP populations. 
Treatment comparisons for all continuous secondary endpoints will be conducted using a MMRM like the 
one described for the primary endpoint. These analyses will be done for both the FAS and PP populations. 
Safety Analyses 
The Safety population will be used for the analysis of safety data (AEs, exposure to study treatment, 
clinical laboratory values, vital signs, and ECG). 
Adverse events will be coded with the Medical Dictionary for Regulatory Activities (MedDRA) and 
WHODrug Global B3 March 2021. Treatment-emergent adverse events (TEAEs) are defined as AEs with 
an onset date on or after the date of first administration of study treatment and before the date of last 
administration of study treatment + 30 days. Treatment-emergent adverse events will be presented by 
system organ class and preferred term in frequency tables. Patients with multiple AEs will be counted 
only once within each preferred term and system organ class. Key patient information for patients with an 
AE with an outcome of death, patients with SAEs, and patients with an AE leading to discontinuation of 
study treatment will be listed. 
Laboratory data (hematology, serum chemistry, coagulation, and urinalysis) will be converted to Système 
International (SI) units for reporting and processing purposes. Absolute values and changes from Baseline 
will be presented descriptively. Laboratory data outside study specific reference ranges will be listed. 
Vital signs and ECG parameters will be presented descriptively. 
ATI-450 Drug Concentrations and Pharmacokinetic Analyses 
Plasma concentrations of ATI-450 and its primary circulating metabolite, CDD-2164, will be summarized 
by day and sample. Concentration versus time since dose (Days 1, 8, 15, 29, 43, 57, and 85) will be 
displayed by linear scale.  
 
 

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Handling of Missing Data 
Missing data will not be imputed for the safety summaries, or the efficacy summaries conducted on the 
PP population. All efficacy analyses conducted on the FAS population will use  a last observation carried 
forward (LOCF) imputation.  Additionally, a sensitivity analysis will be conducted for categorical 
endpoints conducted on the FAS using a non-responder imputation method. Further details regarding the 
imputation of data that are missing or following intercurrent events will be provided in the SAP. 
Data Monitoring Committee: 
An independent DSMB will convene to monitor interim safety data. Details regarding DSMB 
membership, responsibilities, and meeting frequency are outlined in the DSMB Charter. 
 
1.2 
Schema 
Figure 1 
Study Schema 
 
Abbreviations: BID =twice daily 
 
 

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1.3 
Schedule of Assessments 
Table 1 
Schedule of Assessments 
Assessment 
Screening 
Visit 1 
Day -28 
to Day -1 
Baseline 
Visit 2 
Day 1j 
 
Visit 3 
Day 8j 
Visit 4 
Day 15 
Visit 5 
Day 29 
Visit 6 
Day 43 
Visit 7 
Day 57 
Visit 8 
Day 85  
(Week 
12/ET) 
Follow-up 
Visit 9 
30 days 
Visit Window 
NA 
NA 
±1 day 
(+7 days) 
Assessmentsi 
 
Informed Consent  
X 
 
 
 
 
 
 
 
 
Eligibility Review 
X 
X 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical History; HS and 
Other Current Medical 
Conditions  
X 
 
 
 
 
 
 
 
 
Lesion Count including AN 
and draining fistula (tunnels) 
count 
X 
X 
X 
X 
X 
X 
X 
X 
X 
NRS30 – Patient’s Global 
Assessment Skin Pain 
 
X 
X 
X 
X 
X 
X 
X 
 
DLQI Scale 
 
X 
 
 
X 
 
X 
X 
 
Hurley Stage Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Protocol ATI-450-HS-201 - Version 5.0 
 
21 
Assessment 
Screening 
Visit 1 
Day -28 
to Day -1 
Baseline 
Visit 2 
Day 1j 
 
Visit 3 
Day 8j 
Visit 4 
Day 15 
Visit 5 
Day 29 
Visit 6 
Day 43 
Visit 7 
Day 57 
Visit 8 
Day 85  
(Week 
12/ET) 
Follow-up 
Visit 9 
30 days 
Visit Window 
NA 
NA 
±1 day 
(+7 days) 
Assessmentsi 
 
HS-PGA Scale 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECGa 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signsb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Body Weight, BMI (derived) 
X 
 
 
 
 
 
 
X 
 
Full Physical Exam, Including 
Height 
X 
 
 
 
 
 
 
 
 
Targeted Physical Exam 
 
X 
X 
X 
X 
X 
X 
X 
X 
Lesion Photography (optional) 
 
X 
 
 
X 
 
 
X 
 
Laboratory Assessments: 
Hematology, Coagulation, 
Chemistry, Lipids, and 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
hsCRP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HIV and Hepatitis B & C 
Screen 
X 
 
 
 
 
 
 
 
 
SARS-CoV-2 Testing 
X 
X 
 
 
 
 
 
 
 
QuantiFERON Gold Test for 
TB 
X 
 
 
 
 
 
 
 
 

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Protocol ATI-450-HS-201 - Version 5.0 
 
22 
Assessment 
Screening 
Visit 1 
Day -28 
to Day -1 
Baseline 
Visit 2 
Day 1j 
 
Visit 3 
Day 8j 
Visit 4 
Day 15 
Visit 5 
Day 29 
Visit 6 
Day 43 
Visit 7 
Day 57 
Visit 8 
Day 85  
(Week 
12/ET) 
Follow-up 
Visit 9 
30 days 
Visit Window 
NA 
NA 
±1 day 
(+7 days) 
Assessmentsi 
 
Serum Pregnancy (WOCBP 
Only) 
X 
 
 
 
 
 
 
 
 
Urine Pregnancy (WOCBP 
Only) 
 
X 
X 
X 
X 
X 
X 
X 
X 
PK Blood Sampling 
 
Xc 
Xc 
Xd 
Xd 
Xd 
Xd 
Xc 
 
Dispense Study Treatment 
 
X 
X 
X 
X 
X 
X 
 
 
Administration of Morning 
Dose of Study Treatment in 
Clinic 
 
X 
X 
X 
X 
X 
X 
Xg 
 
Study Treatment 
Accountability 
 
 
X 
X 
X 
X 
X 
X 
 
Adverse Eventsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior and Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Protocol ATI-450-HS-201 - Version 5.0 
 
23 
AE=adverse event; AN=abscess and inflammatory nodule count; BMI=body mass index; DLQI=Dermatology Life Quality Index; ECG=electrocardiogram; 
EOS=end of study; ET=early termination; HIV=human immunodeficiency virus; HS=hidradenitis suppurativa; hsCRP=high sensitivity C-reactive protein; 
HS-PGA=Physician Global Assessment Scale;  mRNA=messenger RNA; NRS30= Numerical Rating Scale for Patient's Global Assessment of Skin Pain; 
PD=pharmacodynamic; PK=pharmacokinetic; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; TB=tuberculosis; WOCBP=women of 
childbearing potential. 
a. 
Triplicate 12-lead ECGs will be performed at least 30 seconds apart, in a supine position, after resting for at least 10 minutes (without external 
stimulation, e.g., talking, TV, noise) and submitted for central reading. Screening ECGs will be collected prior vital signs and blood samples. On Day 1 
and 8, ECGs will be taken predose and 2 hours postdose. Patients not fasting on Day 1 and 8 will have an additional 4 hr postdose ECG. On Days 15, 
29, 43, 57, and 85 ECGs will be performed as the last assessment in the clinic (as close to Cmax). See Section 8.2.3 for additional details on collection 
parameters. 
b. Vital signs are to be taken before blood collection for laboratory tests. See Section 8.2.2 for additional details on collection parameters. 
c. 
PK blood sampling times on Days 1, 8, and 85 will occur predose and 2 hours after the morning dose. Patients not fasting on Days 1 and 8 will have an 
additional PK sample collected at 4 hours postdose. If the patient objects to both blood draws at the 2hr and 4hr timepoint, the 4hr PK sample is more 
important to collect. Patients must remain in the clinic until 30 minutes after the morning postdose PK blood sampling is completed. See Section 8.5 for 
additional details on collection parameters. 
d. PK blood sampling will occur prior to the morning dose on Days 15, 29, 43, and 57. See Section 8.5 for additional details on collection parameters. 
 
 
 
 
 
 
g. The last dose of study treatment will be administered in the clinic on Day 85. The second dose of study treatment is not to be administered on Day 85.  
h. Serious AE reporting will start at the time of consent. Any AE that occurs between the time of consent and prior to dosing on Day 1 will be recorded as 
medical history. Treatment-emergent AEs will be collected following the first dose of study treatment on Day 1 through the Follow-up Visit (30 days 
after the last administration of study treatment) (Section 5.5). 
i. 
Unscheduled visits are allowed, as deemed necessary by the Investigator, in the event that assessments need to be repeated (eg, lab draws), safety 
follow-up needs to be conducted, or additional dispensing activities need to occur. 
j. 
Patient should be fasted for visits on Days 1 and 8, defined as 8 hours since last food. A snack is permitted 2 hours after the morning dose. 

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Protocol ATI-450-HS-201 - Version 5.0 
24 
2.0 INTRODUCTION 
2.1 
Study Rationale 
Hidradenitis suppurativa is a chronic inflammatory disease primarily affecting apocrine-gland-
rich regions of the body such as the axillary and groin areas. The pathophysiology of HS is 
complex and has not been clearly defined. The primary defect in HS involves occlusion of hair 
follicles, which leads to dilatation and rupture. The resulting spillage of follicular contents into 
the surrounding dermis induces a chemotactic response from neutrophils and lymphocytes and 
inflammation of the hair follicle leads to innate and adaptive immune dysregulation. An 
upregulation of various cytokines, such as TNF-α, IL-1, IL-6, IL-8, IL-17, IL-23, and other 
molecules appears to be important in the pathophysiology of this inflammatory condition.  
The study treatment, ATI-450, is an orally available, novel, potent, and selective small molecule 
inhibitor of the p38α MAPK/MK2 inflammatory signaling pathway being developed for 
treatment of inflammatory disorders. The p38 MAPK pathway offers great potential in the 
treatment of inflammatory diseases such as HS. By targeting MK2, which is downstream from 
p38, it is believed that ATI-450 can effectively and safely inhibit the inflammatory pathways 
without substantially impacting anti-inflammatory pathways. 
 
 
 
  
This study is being conducted to determine the efficacy, safety, tolerability, PK, and PD of 12 
weeks of ATI-450 exposure in patients with moderate to severe HS. This important data will 
further describe the efficacy and safety of ATI-450 in a relevant patient population. 
2.2 
Background 
Hidradenitis suppurativa, also called acne inversa, is a chronic inflammatory skin disease that 
affects apocrine gland-bearing skin in the axillae, groin, and under the breasts. It is characterized 
by persistent or recurrent boil-like nodules and abscesses that culminate in a purulent discharge, 
sinuses, and scarring.  
A retrospective analysis of 48 million unique US patients revealed an overall HS incidence of 
0.10% in the sample population, which comprised 47,690 patients with HS (26.2% men and 
73.8% women) (Garg et al, 2017).  
While anti-TNF-α inhibitor therapy has improved treatment of HS, there remains a need for 
effective and well tolerated therapies. 

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Protocol ATI-450-HS-201 - Version 5.0 
25 
The Sponsor is developing ATI-450, an orally available, small molecule inhibitor of the p38α 
MAPK/MK2 inflammatory signaling pathway. The p38 MAPK signaling pathway has long been 
a target for therapeutic intervention for inflammatory diseases owing to its involvement in the 
regulation and the expression of multiple cytokines and other inflammatory signals (Saklatvala, 
2004; Schett, 2008). Key inflammatory cytokines driven by this pathway include TNF-α as well 
as IL-1α, IL-1β, and IL-6. The involvement of these cytokines in a variety of diseases, including 
rheumatoid arthritis (RA) and HS, has been demonstrated by successful treatment of 
inflammatory disease with anti-TNF-α monoclonal antibodies, antagonists of the IL-1 receptor, 
anti-IL-1β monoclonal antibodies, and anti-IL-6 receptor monoclonal antibodies (Ruocco 2009; 
Patel 2015; Kimball et al 2016; Kullenberg 2016; Broderick 2015; Kanni 2018; Maarouf 2018). 
However, a drawback of biologics is that they specifically target single cytokine targets in a 
disease in which multiple cytokines have a pathophysiological role. In addition, biologics require 
self-administered injections, and many patients prefer oral options. Thus, identification of orally 
available small molecule therapeutics would add to the available treatment modalities. 
Study treatment ATI-450 has a novel mechanism of action in that it targets the high affinity 
docking interaction between p38α MAPK and MK2 (Wang 2018). Upon binding to the interface 
created upon formation of this bimolecular complex, ATI-450 blocks MK2 phosphorylation by 
p38 MAPK and thereby the downstream MK2-mediated inflammatory drive. Study treatment 
ATI-450 shows low potency for inhibition of p38α phosphorylation/activation of alternate 
substrates and is selective across the human kinome.  
The Sponsor is developing ATI-450 for potential treatment of inflammatory disorders in which 
anti-TNF-α and anti-IL-1β biotherapeutics have shown themselves to be efficacious. Additional 
information regarding nonclinical and clinical experience with ATI-450 can be found in the 
Investigator’s Brochure (IB). 
2.3 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol ATI-450-HS-201 - Version 5.0 
 
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3.0 OBJECTIVES AND ENDPOINTS 
Table 2 
Study Objectives and Endpoints 
Objectives 
Endpoints 
 
 
Primary 
 
• 
To assess the efficacy of ATI-450 in patients with 
moderate to severe HS 
• 
Change from Baseline in inflammatory 
nodule/abscess count at Week 12 
Secondary 
 
• 
To assess the efficacy, and safety of ATI-450 in 
patients with moderate to severe HS 
• 
Percentage of patients achieving HiSCR at 
Week 12. 
 
HiSCR is defined as at least a 50% reduction from 
Baseline in the total abscess and inflammatory 
nodule (AN) count, with no increase in abscess or 
draining fistula counts. 
 
• 
Change from Baseline in IHS-4 over time for the 
12-week treatment period. 
• 
Percentage of patients achieving at least a 30% 
reduction and at least 1 unit reduction from 
Baseline in the numerical rating scale (NRS30) in 
Patient's Global Assessment of Skin Pain at 
Week 12 among patients with Baseline NRS ≥3. 
 
NRS30 is evaluated based on worst skin pain in a 
24-hour recall period (maximal daily pain). 
 
• 
Change from Baseline in Hidradenitis 
Suppurativa-Physician Global Assessment (HS-
PGA) over time for the 12-week treatment period. 
• 
Change from Baseline in Dermatology Life 
Quality Index (DLQI) over time for the 12-week 
treatment period. 
 
The DLQI is a 10-item validated questionnaire 
used to assess the impact of HS disease symptoms 
and treatment on quality of life (QoL). It consists 
of 10 questions evaluating impact of skin diseases 
on different aspects of a patient's QoL over the 
prior week, including symptoms and feelings, 
daily activities, leisure, work or school, personal 
relationships, and the side effects of treatment. 
 
 

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Protocol ATI-450-HS-201 - Version 5.0 
 
29 
Objectives 
Endpoints 
Secondary (continued) 
 
 
• 
Change from Baseline in Hurley Stage over time 
for the 12-week treatment period. 
• 
Incidence of adverse events (AEs), serious AEs 
(SAEs), laboratory value abnormalities, 
electrocardiogram (ECG) abnormalities, vital 
signs abnormalities 
• 
To assess the PK of ATI-450 in patients with 
moderate to severe HS 
• 
Trough ATI-450 and metabolite (CDD-2164) 
concentrations at clinic visits. On Day 1, 8, and 85 
trough and 2-hour post dose will be collected.  
Exploratory 
 
• 
To assess the pharmacodynamics (PD) of ATI-450 
in patients with moderate to severe HS 
 
 
  
 
 
 
 
 

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Protocol ATI-450-HS-201 - Version 5.0 
30 
4.0 STUDY DESIGN 
4.1 
Overall Design 
This is a Phase 2a, randomized, double-blind, placebo-controlled study to investigate the 
efficacy, safety, tolerability, PK, and PD of ATI-450 50 mg BID versus placebo in patients with 
moderate to severe HS.  
• The study will consist of an up to 28-day Screening Period, a 12-week treatment period, 
and a 30-day follow-up period. The total duration of the study for patients remaining until 
their final follow-up assessment will be up to 21 weeks. 
• The Investigator will obtain signed informed consent from the patient before any study 
procedures are performed. 
• During the Screening Period, each patient will be required to have all assessments 
performed as outlined in the SoA (Table 1).  
• Results for all the Screening assessments must be available at the time patient eligibility is 
reconfirmed prior to randomization and dosing. 
• Patients whose eligibility is confirmed at Baseline will be randomized in a 1:1 ratio to 
receive either ATI-450 tablets (50 mg BID) or matching placebo tablets BID. Study 
treatments will be administered orally for 12 weeks.  
• Patients will attend clinic visits on Days 1, 8, 15, 29, 43, 57, and 85 for safety, efficacy, 
PK, and PD assessments. The morning dose of study treatment will be administered in the 
clinic on each study visit day. 
• On Day 85 (Week 12), patients will complete the EOS assessments. A safety follow-up 
visit will be conducted 30 days after the last dose of study treatment for patients who 
completed the treatment period, as well as those who discontinue early.  
• The study is randomized and double-blinded to prevent bias in treatment allocation and in 
the assessment of treatment effect. 
4.2 
Scientific Rationale for Study Design 
A randomized, double-blind, placebo-controlled study design is a conventional and well-
established design to assess efficacy and safety of new treatments in HS.  
Sample size justification is provided in Section 9.3. 
4.3 
 
 
 
 
 
 

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Protocol ATI-450-HS-201 - Version 5.0 
31 
 
 
 
 
 
 
 
 
 
 
 
4.4 
End of Study Definition 
A patient is considered to have completed the study if he/she has completed all study visits. For 
the purposes of this study, the EOS date for an individual patient will be the last date of 
successful contact for study purposes including nonclinic follow-ups (eg, phone call for patients 
lost to follow-up, continued follow-up on outstanding AE/SAE, etc). 
The end of the study is defined as the date of the last visit or date of last procedure of the last 
patient in the study. 

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Protocol ATI-450-HS-201 - Version 5.0 
32 
5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Patients must meet the following criteria to be eligible for participation in the study: 
1. Able to comprehend and be willing to sign the IRB-approved patient ICF prior to
administration of any study-related procedures.
2. Patient with HS for at least 1 year (365 days) prior to Baseline visit; duration of disease as
determined via Investigator review of patient medical history.
3. Patient must have stable HS for at least 60 days prior to Screening visit and at Baseline visit
as determined via Investigator review of patient medical history.
4. Total AN count of ≥5 at Baseline visit. Abscesses and nodules must have the following signs
of inflammation. (Inflammatory nodules should be raised):
a.
Clinical evidence of erythema and/or warmth.
b. Clinical evidence of pain/tenderness.
5. Has HS lesions present in at least 2 distinct anatomical areas at Screening and Baseline.
(Bilateral involvement of the same area counts as 2 areas, eg, involvement of right and left
axilla.)
6. Draining fistula count of ≤20 at Baseline visit.
7. Male or nonpregnant, nonbreastfeeding female patients between 18 and 70 years of age,
inclusive, at the time of signing the ICF.
a.
Heterosexually active female patients who are of childbearing potential must use
2 methods of highly effective contraception, 1 of which must be a physical barrier, for
the duration of the study and for 30 days after the last dose (see Appendix 6).
b. Heterosexually active male patients of childbearing potential with a female partner of
childbearing potential must agree to use a condom plus another highly effective form
of birth control for the duration of the study and for 90 days after the last dose (see
Appendix 6).
8. Female patients of childbearing potential must have a negative serum pregnancy test at
Screening and a negative urine pregnancy test prior to dosing on Day 1.
9. Screening laboratory evaluations (hematology, chemistry, coagulation, and urinalysis) must
fall within the normal range of the central laboratory’s reference ranges unless the results
have been determined by the Investigator to not be clinically significant.
10. No COVID-19 vaccination or booster within the 4 weeks prior to randomization. Note:
COVID vaccination is highly encouraged but not required.

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Protocol ATI-450-HS-201 - Version 5.0 
 
33 
5.2 
Exclusion Criteria  
A patient who meets any of the following exclusion criteria will not be eligible for the study: 
1. Patient has a history of active skin disease other than HS that could interfere with the 
assessment of HS. 
2. Patient has an uncontrolled non-immunoinflammatory disease that may place the patient at 
increased risk during the study or impact the interpretation of results, eg, previous 
malignancy, previous venous thromboembolism. 
3. History or evidence of active tuberculosis, irrespective of prior or current treatment status; or 
current or prior untreated latent tuberculosis. Note: Prior latent tuberculosis with completed 
treatment is not an exclusion. 
4. Known hypersensitivity to ATI-450. 
5. Patient is an alcoholic, or has a history of alcoholism, alcoholic liver disease, or other chronic 
liver disease. 
6. Active infection with SARS-CoV-2 virus. 
7. Positive for HIV or hepatitis B or C. Note: Patients with hepatitis B surface antibody without 
the presence of hepatitis B surface antigen will be allowed to participate. Patients with 
hepatitis C antibody positive can have Hepatitis C viral load tested, if the Hepatitis C virus is 
undetectable and the patient has been off antivirals for 6 months, he/she may be enrolled in 
the study.  
8. Tests performed at a central laboratory at Screening that meet any of the criteria below (out 
of range labs may be rechecked once, after consultation with the Medical Monitor, before 
patient is considered a screen failure): 
a. White blood cell count <3.0×103 cells/mm3. 
b. Absolute neutrophil count <1.5×103 cells/mm3. 
c. Lymphocyte count <0.5×103 cells/mm3. 
d. Platelet count <100×103 cells/mm3. 
e. Hemoglobin <10 g/dL. 
f. Aspartate aminotransferase (AST) or ALT ≥1.5 × ULN. 
g. Total bilirubin level >2 × ULN unless patient has been diagnosed with Gilbert 
syndrome and this is clearly documented. 
h. Estimated glomerular filtration rate (eGFR), <40 mL/min/1.73 m2 based on 
Modification of Diet and Renal Disease formula. 
9. Any clinically significant laboratory abnormality that would affect interpretation of study 
data or safety of the patient’s participation in the study, per judgment of the Investigator. 

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Protocol ATI-450-HS-201 - Version 5.0 
34 
10. Clinically significant abnormal findings other than HS from PE conducted at Screening visit 
(Visit 1) and at Baseline visit (Visit 2) that may affect the interpretation of study data or the 
safety of the patient’s participation in the study, per the judgment of the Investigator. 
11. Clinically important history of a medical disorder that would compromise patient safety or 
data quality, per judgment of the Investigator. 
12. Blood pressure levels (in semi-supine position after at least 5 minutes rest): <90 mmHg or 
>150 mmHg for systolic BP or <40 mmHg or >90 mmHg for diastolic BP. 
13. Patient has experience with >2 biologics, >1 JAK inhibitor, or a combination of 1 biologic 
experience and 1 JAK inhibitor. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
15. Are currently receiving corticosteroids at doses greater than 10 mg per day of prednisone (or 
equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 
2 weeks of the Screening visit. 
16. Have been using prescription topical therapies for treatment of HS within 14 days prior to 
Baseline visit. 
17. Oral or topical tetracycline class antibiotics for treatment of HS are allowable if patient is on 
a stable dose for 4 weeks prior to Baseline and willing and able to maintain the stable dose 
for duration of study. 

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Protocol ATI-450-HS-201 - Version 5.0 
35 
 
 
 
 
 
 
20. Patients with history of stroke. 
21. Significant active cardiac disease, in the past 6 months, that would affect interpretation of 
study data or the safety of the patient’s participation in the study, per judgment of the 
Investigator. This includes myocardial infarction or unstable angina, acute coronary 
syndrome, or heart failure with New York Heart Association Class II, III or IV symptoms. In 
addition, patients with a personal or family history of congenital long QT syndrome, 
Torsades de Pointes, sustained or symptomatic VT, or unexpected sudden cardiac death. 
22. Patients with any of the following Baseline predose ECG findings: 
a. Mean QTcF >450 msec as averaged on triplicate ECG; 
b. ECG or historical evidence of the Wolff-Parkinson-White Syndrome (unless 
ablated); 
c. If atrial fibrillation or flutter is present, the mean ventricular response must be < 
90 BPM and the patient must be anticoagulated according to national guidelines; 
and/or 
d. Any other finding that is considered clinically significant. 
23. Any dermatologic surgery or procedure in the past 90 days prior to Screening. 
24. Known exposure to an individual with a confirmed, active diagnosis of COVID-19 at any 
time during the Screening Period. 
25. Participated in another ATI-450 clinical study. 
26. History of clinically significant drug abuse within 2 years prior to Screening. Note: 
Marijuana use is allowed, if not considered substance abuse by the investigator. 
27. Uncontrolled hypokalemia (<3.8mmol/L), or uncontrolled hypomagnesemia (< LLN) 
 
 
 
 
 
 
 

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Protocol ATI-450-HS-201 - Version 5.0 
 
36 
5.3 
Lifestyle Considerations 
There are no other lifestyle considerations (such as dietary or physical activity restrictions) for 
this study. 
5.4 
Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently randomized. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure patients to meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE. 
5.4.1 
Retesting During Screening 
Laboratory parameters and/or assessments that are included in the Screening procedures 
(Table 1) may be repeated once during the Screening Period in consultation with the Medical 
Monitor. Retesting will be allowed when the significance of a laboratory result is unclear, and 
the retest will help interpretation and decision-making for entry to the study. Retesting will not 
be undertaken when the laboratory results clearly indicate clinically significant disease that could 
impact study interpretation or the safety of a study patient during participation. 
The most current result prior to randomization is the value by which study inclusion will be 
assessed, as it represents the patient’s most current clinical state. 
5.4.2 
Rescreening 
This study will permit 1 rescreening of a patient who has failed 1 or more inclusion or exclusion 
criteria. Consultation with the medical monitor will be needed to identify whether rescreening is 
clinically relevant. If rescreened, the patient must sign a new ICF and the same Patient Number 
will be assigned. 
For patients who are rescreened, consult with the Medical Monitor to confirm which parameters 
and/or assessments that were collected as part of the original Screening Period procedures may 
be utilized, if any. 
5.5 
COVID-19 Guidance 
5.5.1 
COVID-19 Vaccination and Treatment Guidance 
Prior to the Study: 
While not a precondition for study participation, it is strongly recommended that patients receive 
vaccination against COVID-19 prior to enrolling in the study and initiation of study treatment. If 
possible, the first dose of study treatment should be given at least 4 weeks after completion of the 

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Protocol ATI-450-HS-201 - Version 5.0 
 
37 
patient’s COVID-19 vaccination regimen (or booster shot, if applicable). 
 
During the Study: 
Prior to proceeding with COVID-19 vaccination during the study period, each patient’s specific 
situation should be discussed with and approved by the study medical monitor. Where possible, 
the timing of vaccination should be planned so that a vaccination is not administered during the 
study treatment period. 
 
Investigators and patients should consider the schedule of their COVID-19 vaccination (if 
applicable), including potential booster shots, when planning the timing of their study 
participation. Where possible, the timing of vaccination should be planned so that a booster 
vaccination is not administered during the study treatment period. Ideally, administration of a 
COVID-19 booster vaccine (if applicable) should be given at least 4 weeks prior to the first dose 
of study treatment. 
If unavoidable, vaccination can proceed during the study, but every effort should be made to 
avoid administration during the final month of the treatment period, if possible. It should be 
noted that the effect of ATI-450 on the response to COVID-19 vaccination is unknown. The 
COVID-19 vaccine may lead to AEs (fever, chills, etc.), which will need to be captured and 
distinguished as related to vaccine versus ATI-450. 
Patient’s may be treated for COVID-19 infections as needed, including with monoclonal 
antibody therapy, as long as the treatment is not a prohibited medication per protocol 
Appendix 5. If a patient is treated with a protocol prohibited medication, then the study drug 
should be discontinued. 
5.5.2 
COVID-19 Testing Guidance 
At the Screening visit (Visit 1) and Baseline visit (Visit 2) prior to the first dose of study 
treatment, all patients must have a nasopharyngeal (preferred) or oropharyngeal swab collected 
to test for the presence of the SARS-CoV-2 virus. The sample will be sent to the study’s central 
lab for analysis by an acceptable diagnostic assay. Patients with positive test results at Visit 1 
will be considered screen failures per the exclusion criteria for the study but may be considered 
for rescreening at a later date following consultation with the study Medical Monitor. 
Patients are allowed to dose with study treatment in the interval between sample collection at the 
Baseline visit and result reporting as long as there is no clinical suspicion of COVID-19 infection 
or patient recent exposure to an individual with a confirmed, active infection.  
If the patient’s results are positive for SARS-CoV-2 following sample collection at Visit 2, the 
patient will need to be notified immediately upon receipt of the results. The patient should be 
advised to begin self-isolation and self-monitoring procedures according to any applicable local, 

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Protocol ATI-450-HS-201 - Version 5.0 
 
38 
state, and/or country-specific health recommendations. Referral to an appropriate health care 
provider for management of the patient’s COVID-19 diagnosis should also be made. The 
patient’s COVID-19 diagnosis will be reported as medical history unless the patient’s clinical 
course progresses such that criterion for SAEs reporting is met (see Appendix 4), in which case, 
all applicable safety reporting procedures will be followed by the site.  
Sites will also have the option to perform an unscheduled test for the SARS-CoV-2 virus at any 
time during the treatment phase of the study should a patient’s clinical presentation necessitate it, 
in the Investigator’s opinion. The same notification and referral procedures, as outlined in the 
preceding paragraphs, should be followed by the site. However, it is expected that any 
COVID-19 diagnosis made from a sample collected after the initiation of study treatment 
administration be reported as an AE per the requirements of Appendix 4 of this protocol. 
In the event that a patient tests positive for the SARS-CoV-2 virus at or after Visit 2, the 
Investigator must consult with the study Medical Monitor to determine if the patient should 
continue with study medication treatment or discontinue from treatment. Determinations will be 
made on a case-by-case basis with the intent to minimize any increased risk for the patient. 

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Protocol ATI-450-HS-201 - Version 5.0 
 
39 
6.0 STUDY TREATMENT 
Study treatment is defined as any investigational drug(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a patient according to the study protocol. 
6.1 
Study Treatment(s) Administered 
Table 3 
Study Treatment Details 
 
Abbreviation: BID=twice daily 
6.2 
Preparation/Handling/Storage/Accountability 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies are reported and 
resolved before use of the study treatment. 
ATI-450 and placebo will be stored under controlled conditions according to the storage 
requirements described on the label(s). 
 
 The Investigator (or designee) will instruct 
patients to store the study treatment in accordance with the instructions on the label(s). 
Only patients enrolled in the study may receive study treatment and only authorized study center 
staff may supply or administer study treatment. All study treatments must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the Investigator and authorized study center 
staff. 
Study Treatment Name: 
 
ATI-450 
Placebo 
Dosage Formulation: 
 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Dosage 
Level(s): 
50 mg BID 
Not applicable 
Route of Administration  
Oral 
Oral 
 Dosing Instructions: 
 
Take 1 tablet by mouth BID 
Take 1 tablet by mouth BID 
Packaging and Labeling 
 
 
 
 
 
Manufacturer 
 
 
 
 

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The Investigator and/or designee is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records). 
The Investigator, a member of the study center staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study treatment using the Drug 
Accountability Form. These forms must be available for inspection at any time. 
Additional instructions regarding study treatment preparation and handling and the final 
disposition of unused study treatment can be found in the Pharmacy Manual. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
All patients will be centrally assigned to randomized study treatment using an Interactive 
Voice/Web Response System (IxRS). Before the study is initiated, access instructions and 
directions for the IxRS will be provided to each study center. 
Study treatment will be dispensed at the study visits summarized in the SoA (Table 1). Refer to 
the study Pharmacy Manual for specific guidelines concerning dispensing and accountability 
procedures for study treatment. 
Patients will be randomized to study treatment in a 1:1 ratio to ATI-450 50 mg BID or placebo. 
This is a double-blind study with limited access to the randomization code. The ATI-450 and 
placebo tablets will be identical in physical appearance. The treatment each patient will receive 
will not be disclosed to the Investigator, study center staff, patient, or Sponsor/designee. The 
treatment codes will be available to a limited number of third-party vendor personnel (IxRS 
administrative personnel, Clinical Supplies Management personnel, and unblinded 
biostatistician) for them to support their functions on the study. 
The IxRS will be programmed with blind-breaking instructions. In case of an emergency, the 
Investigator has the sole responsibility for determining if unblinding of a patient’s treatment 
assignment is warranted. Patient safety must always be the first consideration in making such a 
determination. If the Investigator decides that unblinding is warranted, the Investigator should 
make every effort to contact the study Medical Monitor prior to unblinding a patient’s treatment 
assignment unless this could delay emergency treatment of the patient. If a patient’s treatment 
assignment is unblinded, the study Medical Monitor must be notified within 24 hours after 
breaking the blind. The date and reason that the blind was broken must be recorded in the source 
documentation and electronic case report form (eCRF), as applicable. 
6.4 
Study Treatment Compliance 
The prescribed dosage, timing, and mode of administration may not be changed. Any departures 
from the intended regimen must be recorded in the eCRFs. 

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At each visit, prior to dispensing study treatment, previously dispensed study treatment will be 
retrieved by the Investigator and compliance assessed both through tablet counting and review of 
a dosing diary completed by the patient. Patients exhibiting poor compliance as assessed by 
tablet counts and diary completion should be counseled on the importance of good compliance to 
the study dosing regimen.  
Noncompliance is defined as taking <80% or >120% of study treatment during any evaluation 
period (visit to visit). See Section 8.4 regarding treatment of ATI-450 overdose. 
6.5 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the patient is receiving at the time of enrollment (within 14 days 
before the time of enrollment) or receives during the study must be recorded on the eCRF along 
with: 
• Reason for use; 
• Dates of administration including start and end dates and times (if available); and 
• Dosage information including dose and frequency. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Antibiotic Therapy 
Patients are allowed to continue treatment with antibiotics for HS from the tetracycline class if at 
stable dose. A stable dose is defined as no change for 4 weeks prior to Baseline visit. The patient 
must be willing and able to maintain stable dose for duration of study. Allowable oral and topical 
antibiotics from the tetracycline class are: tetracycline, doxycycline, or minocycline.  
Antiseptic Use 
If previously used prior to entry into the study, patients may continue cleansing HS lesions with 
their daily antiseptic wash, such as chlorhexidine gluconate, triclosan, benzoyl peroxide, or dilute 
bleach in bathwater. Use of new antiseptic wash during the study is not permitted. 
Wound Care 
Concomitant use of wound care dressings on HS wounds is allowed (excluding topical 
antibiotics and other prohibited medications). 
 
 
 
 

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6.5.1 
Rescue Medicine 
Rescue therapy for HS is not permitted except for the use of acetaminophen (as per label) and 
nonsteroidal anti-inflammatory drugs to treat breakthrough pain and discomfort during the study. 
Neither the study center nor the Sponsor will supply rescue medication.  
6.6 
Dose Modification 
No dose modifications are permitted in this study. 
6.7 
Treatment after the End of the Study 
The Sponsor will not provide any additional care to patients after they leave the study because 
such care should not differ from what is normally expected for patients with HS.  

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7.0 DISCONTINUATION OF STUDY TREATMENT AND 
PATIENT DISCONTINUATION/WITHDRAWAL  
7.1 
Discontinuation of Study Treatment  
Criteria for discontinuation due to abnormal liver function, neutrophil laboratory values, CK 
laboratory values, and skin toxicity are outlined below. In the event that a patient discontinues 
treatment with study treatment prematurely, it is preferred (so as to minimize missing data) that 
the patient be given the opportunity to complete the remainder of his/her expected study visits 
per the SoA (Table 1) rather than being discharged from the study in full. 
7.1.1 
Liver Function 
Study intervention will be discontinued for a patient if liver chemistry stopping criteria are met 
and confirmed upon repeat testing. Samples for confirmation testing should be collected as soon 
as possible after receipt of initial laboratory results indicative of the need to monitor for stopping 
criteria. If ALT or AST is ≥5 × ULN, then study treatment should be held while confirming. 
Liver Chemistry Stopping Criteria and Increased Monitoring Algorithm 
 
Abbreviations: ALT=alanine transaminase; AST=aspartate transaminase, INR=international normalized ratio; 
SAE=serious adverse event; Tbili=total bilirubin, ULN=upper limit of normal. 
Note: The red star indicates the starting point. 
 

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Liver Safety: Suggested Actions and Follow-up Assessments can be found in Appendix 7. 
7.1.2 
Neutrophil Laboratory Values 
Withdraw study treatment if absolute neutrophil count drops below 500 cells/mm3 and is 
maintained below 500 cells/mm3 on a confirmatory sample. 
7.1.3 
Creatine Kinase Laboratory Values  
Withdraw study treatment if an elevation of CK >5 × ULN is observed on repeat testing without 
benign explanation (eg, recent exercise) occurs. 
7.1.4 
Skin Toxicity 
Withdraw study treatment in the case of any severe skin reaction which is considered to be 
related to the study treatment. 
If drug is stopped for reasons as described above, restarting the study drug is not allowed. 
7.2 
Temporary Discontinuation  
7.2.1 
Unrelated Adverse Events or COVID-19 Diagnosis 
If a drug is stopped temporarily due to a clearly unrelated adverse event, for example, treatment 
of a fracture caused by a motor vehicle accident or COVID-19 infection, dosing may be 
reinitiated, after discussion with the Medical Monitor, if the temporary discontinuation was 
shorter than a maximum of 14 days in the total 12-week treatment period. In exceptional 
circumstances, medical monitor may allow dosing to be resumed with a gap of up to 21 days. In 
all cases, if the dosing gap is in excess of 21 days, dosing should be discontinued permanently.  
In case of a COVID-19 infection, consult study Medical Monitor to discuss risk/benefit 
considerations of patient continuing or discontinuing study medication treatment. 
7.2.2 
ECG Criterion for Drug Discontinuation  
In the event that a study ECG assessment demonstrates either of the bulleted criteria below (upon 
local review by the Investigator), a PK and lab sample (serum potassium and magnesium levels) 
should be drawn. The ECG should be repeated within 30 minutes. Patient study treatment dosing 
should be interrupted until the results of the centrally read cardiologist report are received and 
the study Medical Monitor should be notified: 
• QTcF (average of triplicate set) >500 msec 
• Change from Baseline QTcF (average of triplicate set) >60 msec 
 
 

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7.3 
Rechallenge 
Rechallenge is allowed in only limited circumstances when the drug is temporarily stopped, as 
noted in Section 7.2. Once the drug is permanently stopped, no rechallenge is allowed. 
7.4 
Patient Discontinuation/Withdrawal from the Study 
All patients will be advised that they are free to withdraw from participation in the study at any 
time, for any reason, and without prejudice. The Investigator also has the right to withdraw 
patients from the study at any time for lack of therapeutic effect that is intolerable or otherwise 
unacceptable to the patient, for intolerable or unacceptable AEs, intercurrent illness, 
noncompliance, with study procedures, administrative reasons, or in the Investigator's opinion, to 
protect the patient's best interest. The Sponsor reserves the right to request the withdrawal of a 
patient due to protocol violations or other reasons.  
• Although a patient is not obliged to give his/her reason(s) for withdrawing prematurely from 
a study, the Investigator should make a reasonable effort to ascertain the reason(s), while 
fully respecting the patient's rights. 
• If the patient withdraws consent, the Investigator must clearly determine and document if the 
patient is making a full and immediate revocation of consent (eg, no additional data 
collection may occur) or if the patient is willing to proceed with additional study procedures 

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to ensure a safe and orderly discharge from the study (eg, completion of Early Termination 
and EOS Visits).  
• If the patient withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
• If a patient withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the study center study records. 
• If there is a medical reason for withdrawal, the patient should remain under the supervision 
of the Investigator until satisfactory health has returned. 
• See the SoA (Table 1) for data to be collected at the time of study discontinuation and 
follow-up and for any further evaluations that need to be completed. 
7.5 
Lost to Follow-up 
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study center.  
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit: 
• The study center must attempt to contact the patient and reschedule the missed visit as 
soon as possible and counsel the patient on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the patient wishes to and/or should continue in 
the study. 
• Before a patient is deemed lost to follow-up, the Investigator or designee must make every 
effort to regain contact with the patient (where possible, 3 telephone calls and, if 
necessary, a certified letter to the patient’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the patient’s medical record. 
• Should the patient continue to be unreachable, he/she will be considered to have 
withdrawn from the study and the last known contact/assessment will be the date of 
discontinuation.  
 

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8.0 STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Table 1).  
• Protocol waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the Medical Monitor immediately 
upon occurrence or awareness to determine if the patient should continue or discontinue 
study treatment. 
• Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• All Screening evaluations must be completed and reviewed to confirm that potential 
patients meet all eligibility criteria. The Investigator will maintain a Screening log to 
record details of all patients screened and to confirm eligibility or record reasons for 
Screening failure, as applicable.  
• Patient Reported Outcomes questionnaires should be completed by patients before study 
medication administration. 
• The site should make every attempt to have the same Investigator complete the below 
assessments throughout the study for each patient. 
• The maximum amount of blood collected from each patient over the duration of the study, 
not including any extra assessments that may be required, will be specified in the ICF. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. 
8.1 
Efficacy Assessments  
8.1.1 
Lesion Counts—Abscess, Nodule and Draining Fistulas (tunnels) 
The location and extent of HS will be assessed and recorded at the study visits outlined in the 
SoA (Table 1) by recording the affected anatomic location(s) of the disease, as well as the 
number of inflammatory and noninflammatory nodules, abscesses, and draining and nondraining 
fistulas in each of the locations (Appendix 8).  
The information regarding location and extent of HS involvement will be used to determine the 
Hurley Stage and to calculate the HiSCR, the Hidradenitis Suppurativa-Physician’s Global 
Assessment Scale (HS-PGA) and the International Hidradenitis Suppurativa Severity Score 
System (IHS-4). 
The following areas will be evaluated at visits specified in the SoA to assess and record the 
extent of HS: 
• left and right axillae 
• left and right inframammary areas 
• intermammary area 

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• left and right buttocks 
• left and right inguino-crural folds 
• perianal area and perineal area, and 
• other (eg, abdominal fold, neck, back). 
8.1.1.1 
Hidradenitis Suppurativa Lesions: 
• Inflammatory lesions: evidence of inflammation (eg, erythema, pain, warmth) 
o Nodule: should be raised, round lesion, can be a pyogenic granuloma-like lesion 
o Abscess: fluid (pus) filled 
• Fistula/Tunnel/Sinus Tract: lesion draining to the skin, can be in direct connection with 
one another or localized closely to one another 
o Draining: if open at skin surface (ulcerated), will sometimes ooze a fluid 
o Nondraining: if not open to the skin surface, will not ooze 
• Non-inflammatory lesion: 
o Non-inflammatory nodule: not inflamed or painful 
8.1.1.2 
Hidradenitis Suppurativa Clinical Response 
Hidradenitis Suppurativa Clinical Response is defined as at least a 50% reduction from Baseline 
in the total AN count, with no increase in abscess and no increase in draining fistula counts 
relative to Baseline. 
The HiSCR is defined by the status of 3 types of lesions (see definitions above):  
• Abscesses 
• Inflammatory nodules 
• Draining fistulas 
The definition for response to treatment based on HiSCR relative to Baseline (Day 1, Visit 2) is:  
• At least 50% reduction in AN count 
• No increase in number of abscesses 
• No increase in number of draining fistulas 

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For this score, patients are defined as achievers or non-achievers. Patient achievers at any 
scheduled timepoint will have a HiSCR defined as at least a 50% reduction in abscess and 
inflammatory nodule count (AN count) and no increase in abscesses and no increase in draining 
fistulas relative to Baseline at that timepoint. 
A patient is considered to be a HiSCR achiever only if all 3 criteria above are fulfilled (Kimball 
et al, 2016b).  
The time required for Investigators to complete the HiSCR ranges from 1 to 2 minutes for 
patients with minimal disease, ie, 5 HS lesions in 2 anatomic locations, up to approximately 30 
minutes for patients with multiple lesions in all 12 anatomic locations. 
8.1.1.3 
International Hidradenitis Suppurativa Severity Score System 
The International Hidradenitis Suppurativa Severity (IHS-4) is a validated tool used to assess HS 
severity. The IHS-4 is calculated based on the clinical signs of HS: inflammatory nodules, 
abscesses and draining tunnels (fistulas and sinuses). The terms sinus tract and tunnel should be 
considered as synonyms of fistula (Daxhelet 2020). 
The IHS-4 score (points) = (number of nodules multiplied by 1) + (number of abscesses 
multiplied by 2) + [number of draining tunnels (fistulas/sinuses) multiplied by 4].  
A score of 3 or less signifies mild HS, a score of 4-10 signifies moderate HS and a score of 11 or 
higher signifies severe HS (Zouboulis et al, 2017). 
8.1.2 
Patient's Global Assessment of Skin Pain 
The NRS30 – Patient’s Global Assessment of Skin Pain will be completed daily by patients 
starting at the Baseline visit through Week 12 as outlined in the SoA (Table 1). On visit days, 
patients will complete the NRS30 – Patient’s Global Assessment of Skin Pain at the study center 
prior to administration of the in-clinic morning dose of study treatment. Site personnel will 
witness the completion of the assessment. 
The severity of the patient’s skin pain will be assessed by completion of a numerical rating scale 
with 0 indicating no pain and 10 indicating the worst pain imaginable in a 24-hour recall period 
(maximal daily pain) (Kimball et al, 2016). Patients should be instructed to complete the 
assessment prior to the morning dose of study medication. 
This questionnaire will be administered electronically and should take approximately 1 minute to 
complete. 
8.1.3 
 Dermatology Life Quality Index 
The Dermatology Life Quality Index (DLQI) is a 10-item validated questionnaire used to assess 
the impact of HS disease symptoms and treatment on QoL. It consists of 10 questions including a 
single “yes/no” question and 9 multiple choice questions with possible responses of “not at all,” 

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“a little,” “a lot,” or “very much.” These questions evaluate the impact of skin diseases on 
different aspects of a patient's QoL over the prior week, including symptoms and feelings, daily 
activities, leisure, work or school, personal relationships, and the side effects of treatment. 
Each question is scored using a 4-point scale which ranges from 0-3 based on a patient’s 
response: not at all/not relevant (0), a little (1), a lot (2) and very much (3) (Basra 2015).  
Question 7, the single yes/no question is two-part question. The first part can be scored based on 
a response of “yes” (3) or “no/not relevant.” If “no/not relevant” is selected, part two of the 
question can be scored based on the following responses: not at all (0) little (1), a lot (2). 
The total score of the DLQI (range of 0-30) is calculated by adding up the scores from each 
question. The higher the score, the greater the impact on a patient’s quality of life.  
This questionnaire will be administered electronically and should take approximately 1 to 
3 minutes to complete. 
8.1.4 
Hidradenitis Suppurativa-Physician’s Global Assessment 
The HS-PGA scale is a 6-point scale used to assess ranges from clear to very severe 
(Hidradenitis Suppurativa Trust, 2018). It is used in clinical trials to measure clinical 
improvement in inflammatory nodules, abscesses and draining fistulas. The 6 stages are based on 
the presence and numbers of nodules, abscesses, and draining fistulas (Kimball et al, 2012). In 
the HS-PGA scale, Investigators will rate the counts of nodules (inflammatory and 
noninflammatory) abscesses and fistulas (both draining and nondraining) and assign a patient to 
1 of 6 categories listed below. 
Severity 
Score 
Definition 
Clear 
0 
0 abscesses, 0 draining fistulas, 0 inflammatory nodules,  
and 0 non-inflammatory nodules 
Minimal 
1 
0 abscesses, 0 draining fistulas, 0 inflammatory nodules,  
and presence of non-inflammatory nodules 
Mild 
2 
0 abscesses, 0 draining fistulas, and 1 to 4 inflammatory nodules  
or  
1 abscess or draining fistula (sum of abscesses and draining fistulas is 
1) and 0 inflammatory nodules 
Moderate 
3 
0 abscesses, 0 draining fistulas, and ≥5 inflammatory nodules  
or  
1 abscess or draining fistula and ≥1 inflammatory nodule or  
2 to 5 abscesses or draining fistulas (sum of abscesses and draining 
fistulas is 2 to 5) and <10 inflammatory nodules 
Severe 
4 
2 to 5 abscesses or draining fistulas and ≥10 inflammatory nodules 

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Very Severe 
5 
>5 abscesses or draining fistulas (sum of abscesses and draining 
fistulas >5) 
 
This questionnaire will be completed electronically by the Investigator and should take 
approximately 1-3 minutes to complete. 
8.1.5 
Hurley Staging System 
The Hurley Staging System is used to assess and grade the progression of HS by placing patients 
in 1 of 3 groups or stages: mild (Hurley Stage I), moderate (Hurley Stage II), or severe (Hurley 
Stage III).  
Hurley Stages defined: 
• Stage I: Abscess formation, single or multiple, without sinus tracts and scarring 
• Stage II: 1 or more widely separated recurrent abscesses with tract formation and scarring 
Stage III: Multiple interconnected tracts and abscesses across the entire area, with diffuse or 
near diffuse involvement 
The Investigator will complete the Hurley Staging assessment for each affected anatomical area 
at each visit specified in the SoA (Table 1). If more than 1 stage is present in an area, the worst 
stage in each area should be applied. 
8.1.6 
Lesion Photography 
Photographs of identified HS lesions will be taken at each study visit specified in the SoA 
(Table 1) for patients who consent to it. Sites will be required to submit the patient’s Baseline 
photographs to Canfield Scientific’s database. Canfield Scientific will supply all investigational 
sites with study-specific laptop and camera equipment to photograph each patient’s identified 
target HS lesion treatment areas (at least 1 HS area but up to 2 unique target areas). Details 
regarding the use of the equipment and how to upload the photographs to the Canfield database 
will be supplied to the sites in the Photography Manual. 
8.2 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA (Table 1). 
8.2.1 
Physical Examinations 
• A complete PE will include, at a minimum, general appearance; skin; eyes; ears, nose, 
throat; head and neck; heart, chest, and lungs; abdomen; extremities; lymph nodes; 
musculoskeletal; neurological; and other body systems, if applicable, for describing the 
status of the patient’s health. 
• A targeted PE will include, at a minimum, signs of HS. 

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• Body weight and height (height at Screening only) will also be measured and recorded. 
Body mass index (BMI) will be calculated electronically in the eCRF. The patient should 
be dressed in lightweight clothing, without shoes. 
• Investigators should pay attention to clinical signs related to previous illnesses. Any new 
abnormalities or worsening of existing abnormalities should be reported as AEs, as 
appropriate (see Section 8.3). 
• See Section 7.0 for discontinuation criteria based on skin toxicity. 
8.2.2 
Vital Signs 
• Vital signs will be measured prior to dosing and immediately following dosing in a 
semi-supine position after ≥ 5 minutes’ rest without distractions (eg, television, cell 
phones). Vital signs (to be taken before blood collection for laboratory tests, when 
applicable) will consist of 1 body temperature measurement, 1 pulse rate measurement, 1 
respiratory rate measurement, and 1 systolic and diastolic BP measurements. One repeat 
will be allowed for any abnormal BP readings.  
• Abnormal, clinically significant vital sign results outside of the 1 allowable repeat will be 
recorded as AEs (see Section 8.3). If known, the underlying etiology for the abnormal 
clinically significant vital sign will be recorded as an AE rather than the vital sign itself. 
• The BP and pulse measurements will be assessed with a completely automated device. 
Manual techniques will be used only if an automated device is not available. 
8.2.3 
Electrocardiograms 
• Triplicate 12-lead ECG will be obtained as outlined in the SoA (Table 1) using an ECG 
machine supplied by the Central ECG Laboratory that automatically calculates the heart 
rate and measures PR, QRS, QT, and QTc intervals. Refer to Section 7.2 for QTc 
withdrawal criteria and any additional QTc readings that may be necessary. 
• Three individual ECG tracings should be obtained as closely as possible in succession, and 
completed in less than 4 minutes.  
• The ECG tracing should clearly identify the patient, include the date and time of the 
assessment, and include the signature and date of the person who made the local 
interpretation; the tracing will be archived at the study site and electronic files sent to the 
Central ECG Laboratory. Abnormal, clinically significant ECG results will be recorded as 
AEs (see Section 8.3). If there is noise or other artifacts, they will be repeated. The QTcF 
intervals should be reviewed based on the automatic read from the ECG machine in real 
time. 
• All ECGs will be transferred and read centrally by a qualified vendor. The ECGs collected 
at the Baseline visit (prior to randomization) should be assessed locally by the Investigator 
for confirmation of eligibility, but the final centrally read report will serve as the document 
of record in the patient’s source chart and from the primary ECG database (EXPERT) for 
the study. 

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• Triplicate 12-lead ECGs will be performed at least 30 seconds apart, in a supine position, 
resting for at least 10 minutes (without external stimulation, e.g., talking, TV, noise) and 
submitted for central reading. Screening ECGs will be collected prior vital signs and blood 
samples. On Day 1 and 8, ECGs will be taken predose and 2 hours postdose. Patients not 
fasting on Day 1 and 8 will have an additional 4 hr postdose ECG. On Days 15, 29, 43, 57, 
and 85 ECGs will be performed as the last assessment in the clinic. 
8.2.4 
Clinical Safety Laboratory Assessments 
See Appendix 3 for the list of clinical laboratory tests to be performed and the SoA (Table 1) for 
the timing and frequency.  
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE Section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those that are not associated with the underlying disease, unless judged 
by the Investigator to be more severe than expected for the patient’s condition. 
See Section 7.0 for discontinuation criteria based on abnormal liver function tests, neutrophil 
values, CK values, or positive SARS-CoV-2 test.  
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 30 days (+7 days) after the last dose of study treatment should be repeated 
until the values return to normal or Baseline or are no longer considered clinically significant by 
the Investigator or Medical Monitor. 
• If such values do not return to normal/Baseline within a period of time judged reasonable 
by the Investigator, the etiology should be identified and the Medical Monitor notified. 
• All protocol-required laboratory assessments, as defined in Appendix 3, must be 
conducted in accordance with the Laboratory Manual and the SoA (Table 1). 
• If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in patient management or are considered 
clinically significant by the Investigator (eg, SAE or AE), then the results must be 
recorded in the eCRF. 
• Serum potassium levels < 3.8 mmol/L will be treated and repeated as will serum 
magnesium levels < LLN. 
8.3 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 4. 
Any AEs will be reported by the patient (or, when appropriate, by a caregiver, surrogate, or the 
patient’s legally authorized representative). 

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The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
patient to discontinue study treatment or the study (see Section 7.0).  
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected at the time points specified in the SoA (Table 1). Serious AE 
reporting will start at the time of consent. Any AE that occurs between the time of consent and 
prior to dosing on Day 1 will be recorded as medical history. All TEAEs will be collected 
following the first dose of study treatment on Day 1 through the Follow-up Visit (30 days after 
the last administration of study treatment). 
All SAEs will be recorded and reported to the Sponsor/designee within 24 hours, as indicated in 
Appendix 4. The Investigator will submit any updated SAE data to the Sponsor within 24 hours 
of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a patient has been discharged from the study, and he/she considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must promptly notify the 
Sponsor/designee. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 4. 
8.3.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the patient is the preferred method to inquire about AE 
occurrences.  
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each patient at 
subsequent visits/contacts. All SAEs and non-serious AEs of special interest (AESIs) (as defined 
in Section 8.3.6), will be followed until resolution, stabilization, the event is otherwise explained, 
or the patient is lost to follow-up up to database lock (as defined in Section 7.5). Further 
information on follow-up procedures is given in Appendix 4. 
8.3.4 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor/designee of an SAE is essential so that 
legal obligations and ethical responsibilities toward the safety of patients and the safety of a 
study treatment under clinical investigation are met.  

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The Sponsor and/or designee has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study treatment under clinical 
investigation. The Sponsor and/or designee will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, IRB, and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor and/or designee will 
review and then file it along with the IB, and will also notify the IRB/IEC, if appropriate 
according to local requirements. 
8.3.5 
Pregnancy 
All patients are required to meet the requirements relating to pregnancy and use of contraception 
described in the inclusion and exclusion criteria (see Sections 5.1 and 5.2, respectively).  
Serum pregnancy testing will be performed only for women of childbearing potential (WOCBP) 
at Screening (Day -28 to Day -1); the result must be negative for the patient to be eligible. A 
urine pregnancy test will be performed only for WOCBP on Day 1 (prior to dosing) and at every 
subsequent study visit through the follow-up visit (Visit 9). The serum pregnancy tests will be 
analyzed by the central laboratory, and the urine pregnancy tests will be analyzed locally. 
• Details of pregnancies in female patients and, if indicated, female partners of male 
patients will be collected after the start of study treatment and until 30 days (ie, 
1 menstrual cycle) after the last dose of study treatment.  
• If a pregnancy is reported, the Investigator should inform the Sponsor/designee within 
24 hours of learning of the pregnancy and should follow the procedures outlined in 
Appendix 6. 
• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
Adverse Events of Special Interest 
The following AEs will be classified as AESI in this study: 
 
 
 
  
 
 
 
 

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8.3.7 
Disease-related Events and/or Disease-related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. Further information on general AE/SAE considerations is given in Appendix 4. 
8.4 
Treatment of Overdose 
For this study, any dose of >3 tablets of ATI-450/placebo per day OR 2 tablets of 
ATI-450/placebo taken at any single dosing time point (eg, morning dose, evening dose) will be 
considered an overdose. The dose of ATI-450 used in this study is based on doses previously 
studied in Phase 1, and plasma exposure is unlikely to exceed previously studied levels if 
patients adhere to dosing instructions. Given the blinded nature of the study, the above 
recommendations make the assumption that each blinded tablet contains 50 mg of ATI-450. 
The Sponsor does not recommend specific treatment for an overdose. 
In the event of suspected or confirmed overdose, the Investigator should: 
• Undertake any supportive measures, as per Investigator judgment. 
• Contact the Medical Monitor immediately. 
• Closely monitor the patient for any AE/SAE and/or laboratory abnormalities until the risk 
is considered to be resolved as agreed with the Medical Monitor. 
• Obtain a plasma sample for PK analysis and any other relevant interventions or 
assessments, if requested by the Medical Monitor (determined on a case-by-case basis). 
• Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions will be made by the Investigator in consultation with the 
Medical Monitor based on the clinical evaluation of the patient. Treatment of confirmed or 
suspected overdose with ATI-450 should consist of clinically appropriate supportive measures. 
Any overdose associated with clinical symptoms will be recorded as an AE or SAE, as 
appropriate. Details of any signs or symptoms and their management should be recorded, 
including details of any treatments administered for the overdose. All overdoses with clinical 
symptoms meeting the SAE criteria must be reported as described in Section 8.3.4. 
8.5 
Pharmacokinetics 
Up to twelve (12) venous blood samples of approximately 2 mL each will be collected for 
measurement of plasma concentrations of ATI-450 and its primary circulating metabolite, 
CDD-2164, as specified in the SoA (Table 1). Instructions for the collection and handling of 
biological samples will be provided by the Sponsor/designee. The actual date and time (24-hour 

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clock time) of each sample will be recorded. The date and time of study treatment administration 
will also be recorded. 
A PK sample will be collected if ECG withdrawal criteria are met, see Section 7.1.1. 
Samples will be used to evaluate the PK of ATI-450. Each plasma sample will be divided into 
2 aliquots (1 each for primary analysis and back-up). Samples collected for analyses of ATI-450, 
CDD-2164 and other metabolite/enantiomer plasma concentrations may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study. 
Genetic analyses will not be performed on these plasma samples. Patient confidentiality will be 
maintained. 
At visits during which blood samples for the determination of PK of ATI-450 will be taken, 
1 sample of sufficient volume can be used. Every effort will be taken to collect the blood 
samples as close as possible to the scheduled time points, but a window of ±10 minutes is 
permitted for each blood draw. In instances where different assessments are due at the same time 
point, they will be performed such that the blood samples for PK analyses will be drawn at the 
correct time (as long as patient safety is not compromised). 
Drug concentration information that may unblind the study will not be reported to study centers 
or blinded personnel until the study has been unblinded. 
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the trial 
master file and Investigator site file but will not constitute a protocol amendment. The IRB/IEC 
will be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICF. 
If a patient refuses blood collection for PK analysis, this will not be considered a protocol 
violation as the PK analysis is a secondary objective. 
Details regarding the processing and shipment of all blood samples can be found in the 
Laboratory Manual. 
8.6 
 
 
 
 
 

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8.7 
Genetics 
Genetics are not evaluated in this study. 
8.8 
Biomarkers 
Biomarkers, other than the pharmacodynamic markers, are not evaluated in this study. 
8.9 
Medical Resource Utilization and Health Economics 
Medical Resource Utilization and Health Economics parameters will not be evaluated in this 
study. 
9.0 STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
The primary statistical hypothesis to be tested in this study is the hypothesis that the ATI-450 
treatment group is superior to placebo for the treatment of HS based upon the 12-week change 
from Baseline in inflammatory nodules and abscesses versus the null hypothesis of no difference. 
This hypothesis will be conducted using a one-sided testing procedure with an alpha level of 
0.05. No adjustment for multiplicity will be made. 
Secondary superiority hypotheses will be tested on the secondary efficacy endpoints to gather 
supportive evidence for the primary hypothesis. These secondary assessments will have the same 
null and alternative hypotheses as the primary and will be tested using a one-sided procedure 
with an alpha level of 0.05. 
9.2 
Sample Size Determination  
Ninety (90) randomized patients will provide 90.3% power to demonstrate the superiority of 
ATI-450 to placebo in the reduction in inflammatory nodules and abscesses at Week 12. This 
power computation assumes that the reduction in the placebo arm will be on average 
2.5 nodules/abscesses and the ATI-450 reduction will be on average 4.75 nodules/abscesses. The 
assumed standard deviation for the number of nodules/abscesses was assumed to be 3.6. These 

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sample size assumptions were based on the values observed in the adalimumab PIONEER I and 
PIONEER II Phase 3 trials (Frew et al, 2020). The assumed reduction in nodules/abscesses for 
ATI-450 was chosen to be slightly less than that shown in the PIONEER I and PIONEER II 
Phase 3 in order to account for the potential impact of dropouts on the efficacy. 
9.3 
Populations for Analyses 
For purposes of analysis, the analysis sets in Table 4 are defined. 
Table 4 
Analysis Sets 
Analysis Set 
Description 
Full Analysis Set (FAS) 
All patients who have been randomized and administered at least 1 dose of 
study treatment. The efficacy analyses will be conducted on the FAS 
population as randomized. 
Per Protocol (PP) 
All randomized patients who remain on study treatment, complete their 
assessments for their Day 85 visit, with no major protocol violations. 
Safety Analysis Set 
All patients randomly assigned to study treatment and who take at least 1 dose 
of study treatment. Patients will be analyzed according to the treatment they 
actually received. 
Pharmacokinetic (PK) 
All patients randomly assigned to study treatment and who take at least 1 dose 
of study treatment and have at least 1 evaluable PK measurement 
Pharmacodynamic (PD) 
All patients randomly assigned to study treatment and who take at least 1 dose 
of study treatment and have at least 1 evaluable PD measurement 
9.4 
Statistical Analyses 
Details of all statistical summaries will be provided in the study-specific SAP. 
All data will be presented by treatment group. Descriptive statistics (number of observations, 
mean, standard deviation, median, minimum, and maximum) will be provided for continuous 
variables, and counts and percentages will be presented for categorical variables. Unless 
otherwise stated, hypothesis tests and corresponding P values will be 1-sided with an alpha level 
of 0.05. No adjustments will be made for multiplicity. 
Baseline is defined as the last nonmissing measurement before, or on the date of first 
administration of study treatment. 

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9.4.1 
Efficacy Analyses 
Table 5 
Efficacy Analyses 
Endpoint 
Statistical Analysis Methods 
Primary 
All efficacy summaries will be conducted on both the FAS and PP populations.  
The primary efficacy analysis will be the treatment comparison of the change from Baseline in 
inflammatory nodules and abscesses at Week 12 in the FAS population. This analysis will be 
conducted within the context of a Mixed Model Repeated Measures (MMRM). This model will 
include factors for treatment group, time, and time by treatment interaction as well as a Baseline 
covariate. Patient identifiers will be included in the model in a manner that allows observations 
within a given patient over time to be treated as repeated measures. Point estimates and 90% 
confidence intervals (CI) for the difference in least square means (LS means) will be provided in 
addition to the 1-sided P values.  
Secondary 
Treatment comparisons for all secondary responder endpoints (percentage of patients meeting HiSCR 
at Week 12, percentage of patients achieving at least 30% reduction from Baseline in NRS30-PGA 
Skin Pain, and percentage of patients who experience at least a 25% increase in AN count with a 
minimum increase of 2 relative to Baseline over the 12-week treatment period) will be conducted 
using a logistic regression applied to each time point separately. The logistic regression will include a 
factor for treatment group and a covariate for Baseline, where appropriate. These analyses will be 
done for both the FAS and PP populations. 
Treatment comparisons for all continuous secondary endpoints will be conducted using a MMRM 
like the 1 described for the primary endpoint. These analyses will be done for both the FAS and PP 
populations. 
Exploratory 
Will be described in the SAP finalized before database lock. 
Abbreviations: AN=abscess and inflammatory nodule; FAS=Full Analysis Set; HiSCR=Hidradenitis Suppurativa 
Clinical Response; NRS30-PGA=Patient’s Global Assessment; PP=Per Protocol; SAP=Statistical Analysis Plan. 
9.4.2 
Safety Analyses 
The Safety population will be used for the analysis of safety data (AEs, exposure to study 
treatment, clinical laboratory values, vital signs, and ECG). 
Adverse events will be coded with MedDRA and WHODrug Global B3 March 2021. The 
TEAEs are defined as AEs with an onset date on or after the date of first administration of study 
treatment and before the date of last administration of study treatment +30 days. Treatment-
emergent adverse events will be presented by system organ class and preferred term in frequency 
tables. Patients with multiple AEs will be counted only once within each preferred term and 
system organ class. Key patient information for patients with an AE with an outcome of death, 
patients with SAEs, and patients with an AE leading to discontinuation of study treatment will be 
listed. 
Laboratory data (hematology, serum chemistry, coagulation, and urinalysis) will be converted to 
Système International units for reporting and processing purposes. Absolute values and changes 
from Baseline will be presented descriptively. Laboratory data outside study specific reference 
ranges will be listed. Vital signs and ECG parameters will be presented descriptively. 

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9.4.3 
Other Analyses  
9.4.3.1 
ATI-450 Drug Concentrations and Pharmacokinetic Analyses 
All PK analyses will be performed using the PK Population. Plasma concentrations of ATI-450 
and its primary circulating metabolite, CDD-2164, will be summarized by day and sample time. 
Concentration versus time since dose (Days 1, 8, 15, 29, 43, 57, and 85) will be displayed by 
linear scale. Population PK modeling and related exposure response modeling may be explored, 
as appropriate. 
9.4.3.2 
 
 
 
  
 
 
9.4.4 
Missing Data 
Missing data will not be imputed for the safety summaries, or the efficacy summaries conducted 
on the PP population. All efficacy analyses conducted on the FAS population will use a LOCF 
analysis. Additionally, a sensitivity analysis will be conducted for categorical endpoints 
conducted on the FAS using the non-responder imputation method. Further details regarding the 
imputation of data that are missing or following intercurrent events will be provided in the SAP. 
9.5 
Interim Analyses  
No interim analysis for efficacy is planned. 
9.6 
Data Monitoring Committee 
An independent DSMB will convene to monitor interim safety data. The DSMB is responsible 
for reviewing and evaluating unblinded safety data at regularly scheduled meetings. The 
Committee may also meet in ad hoc meetings at its discretion as needed in response to events 
occurring in the study. Details regarding DSMB membership, responsibilities, and meeting 
frequency are outlined in the DSMB Charter. 

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10.0 REFERENCES 
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3. Schett G, Zwerina J, Firestein G. The p38 mitogen-activated protein kinase (MAPK) 
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4. Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G. Pyoderma gangrenosum: an 
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safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. 
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10. Kanni T, Argyropoulou M, Spyridopoulos T, et al. MABp1 Targeting IL-1α for Moderate to 
Severe Hidradenitis Suppurativa Not Eligible for Adalimumab: A Randomized Study. 
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