A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Phase I Study Evaluating Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of SOL-116 in Healthy Subjects and Patients With Rheumatoid Arthritis
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Sponsor: Lipum AB

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
Confidential 
Page 1 of 120 
 
Protocol title 
A Randomized, Double-Blind, Placebo-Controlled, First-in-
Human Phase I Study Evaluating Safety, Tolerability and 
Pharmacokinetics of Single Ascending Doses of SOL-116 (a 
Humanized Monoclonal Anti-BSSL Antibody) in Healthy 
Subjects and Patients with Rheumatoid Arthritis 
Protocol ID 
LPM-116-001 
Authors 
 
Document type 
Clinical Study Protocol  
Study Phase 
I 
Document status/version 
Amendment 6 
Date 
05 August 2024 
EudraCT number 
2022-001489-37 
 
Confidentiality Statement 
The information contained in this document, especially unpublished data, is the property of the Sponsor of this 
study, Lipum AB. It is therefore provided to you in confidence as an Investigator, potential Investigator, or 
consultant, for review by you, your staff, and an Independent Ethics Committee or Institutional Review Board. It 
is understood that this information will not be disclosed to others without written authorization from Lipum AB, 
except to the extent necessary to obtain informed consent from those persons to whom the study drug may be 
administered. 
 
 

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
Confidential 
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CONTACT DETAILS 
PRINCIPAL INVESTIGATORS: 
 
 
CHDR 
 
Zernikedreef 8 
 
2333 CL Leiden 
 
The Netherlands 
 
 
 
 
ICON 
 
Van Swietenlaan 6 
 
9728 NZ Groningen 
 
The Netherlands 
 
CLINICAL FACILITIES: 
CHDR 
 
Zernikedreef 8 
 
2333 CL Leiden 
 
The Netherlands 
 
ICON 
 
Van Swietenlaan 6 
 
9728 NZ Groningen 
 
The Netherlands 
 
QPS Netherlands B.V. 
 
Hanzeplein 1, entrance 53 
 
9713 GZ Groningen 
 
The Netherlands 
 
CLINICAL LABORATORY: 
Certe KCL 
 
Borniastraat 34 
 
8934 AD Leeuwarden 
 
The Netherlands 
 
 
Laboratory – chemistry and haematology 
 
AKCL LUMC, E2-P 
 
Albinusdreef 2 
 
2333 ZA Leiden 
 
The Netherlands 
 
 
LUMC Laboratory – Microbiology 
 
Laboratory – Microbiology, E4-P 
 
Albinusdreef 2 
 
2333 ZA Leiden 
 
The Netherlands 
 
BIOANALYTICS (PK, ADA) 
QPS Netherlands B.V. 
 
Petrus Campersingel 123 
 
9713 AG Groningen 
 
The Netherlands 

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
Confidential 
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BSSL ANALYSES: 
BioAgilytix Europe GmbH 
 
Lademannbogen 10, 22339 Hamburg 
 
Germany 
 
CYTOKINE ANALYSES: 
TATAA Biocenter AB 
 
Sofierogatan 3A 
 
SE-412 51 Gothenburg, Sweden 
 
CHEST X-RAY: 
DC klinieken 
 
Krimkade 20 
 
2251 KA Voorschoten 
 
The Netherlands 
 
DATA MANAGEMENT: 
QPS Netherlands B.V. 
 
Hanzeplein 1, entrance 53 
 
9713 GZ Groningen 
 
The Netherlands 
 
PHARMACIES: 
QPS Netherlands B.V. 
 
Petrus Campersingel 123 
 
9713 AG Groningen 
 
The Netherlands 
 
 
Apotheek LUMC, LO-P30 
 
Einthovenweg 6 
 
2333 ZC Leiden 
 
The Netherlands 
 
PHARMACOKINETIC 
QPS, LLC 
ANALYSIS: 
3 Innovation Way, Suite 240 
 
Newark, DE 19711 
 
USA 
 
STATISTICAL ANALYSIS: 
QPS Qualitix Taiwan 
 
5F., No. 12, Sec. 2 
 
Ren-Ai Road 
 
Taiwan 
 
SERIOUS ADVERSE EVENT 
QPS Clinical Services GmbH 
REPORTING: 
Brückenkopfgasse 1, Top 4 und Top 5 
 
8020 Graz 
 
Austria 
 
safetyLPM@qps.com 
 

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
Confidential 
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MEDICAL MONITOR: 
 
 
Medical Monitor 
 
QPS Holding LLC 
 
Ronda de Nelle 22, E2I 
 
15005-A Coruña 
 
Spain 
 
INDEPENDENT ETHICS 
Stichting BEBO 
COMMITTEE: 
Dr. Nassaulaan 10 
 
9401 HK Assen 
 
The Netherlands 
 
SPONSOR: 
Lipum AB 
 
Tvistevägen 48C 
 
SE-907 36 Umeå 
 
Sweden 

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
Confidential 
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1 SIGNATURE PAGE FOR LIPUM AB 
Hereinafter called Lipum AB 
Investigational drug name: SOL-116 
Protocol number: LPM-116-001 
 
 
___________________  
  
Signature 
Date 
Chief Medical Officer 
 
 
 
 
___________________ 
 
Signature 
Date 
Chief Executive Officer 
 
06 augusti 2024 | 20:25 CEST
06 augusti 2024 | 16:38 CEST

QPS code: 210463-CS0382
Clinical Study Protocol
Sponsor code: LPM-116-001
05 August 2024, Amendment 6
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Confidential
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2
Investigational drug name: SOL-116
Protocol number: LPM-116-001
I agree to the terms and conditions relating to this study as defined in this protocol, electronic 
Case Report Form (eCRF), and any other protocol-related documents. I fully understand that 
any changes instituted by the Investigator(s) without previous agreement with the Sponsor
would constitute a violation of the protocol, including any ancillary studies or procedures 
performed on study subjects/patients (other than those procedures necessary for the well-being 
of the subjects/patients).
I agree to conduct this study in accordance with the Declaration of Helsinki and its 
amendments, International Council for Harmonization (ICH) Good Clinical Practice (GCP) 
guidelines and applicable regulations and laws. In particular, I will obtain approval by an
Independent Ethics Committee or Institutional Review Board (IEC/IRB) prior to study start 
and signed informed consent from all subjects/patients included in this study. In addition, I will 
allow direct access to source documents and agree to inspection by auditors from the Sponsor
and Health Authorities. I will ensure that the study drug(s) supplied by the Sponsor are being 
used only as described in this protocol. Furthermore, I confirm herewith that the Sponsor is 
allowed to enter and utilize my professional contact details and function in an electronic 
database for internal purposes and for submission to worldwide Health Authorities.
_
___
Signature
Date
Principal Investigator, CHDR

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
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PROTOCOL CHANGES LOG 
Amendment 6, dated 05 August 2024, original protocol issued 15 September 2022, 
Amendment 1 dated 30 November 2020, Amendment 2 dated 24 February 2023, Amendment 
3 dated 28 July 2023, Amendment 4 dated 29 August 2023, and Amendment 5 dated 06 
December 2023. 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20EC of the European Parliament and the Council of the European Union. 
In this amendment, the inclusion criterion regarding MTX treatment in RA patients and the 
exclusion criterion regarding evidence of tuberculosis in RA patients are updated. Furthermore, 
the Principal Investigator of QPS Netherlands B.V. is removed from the protocol and contact 
details for serious adverse event reporting are updated. 
Section 
Update 
Header  
06 December 2023, 05 August 2024, Amendment 5 6 
Title Page 
Document status/version Amendment 5 6 
Date 06 December 2023 05 August 2024 
Contact Details 
Principal investigators 
 
Hanzeplein 1, entrance 53 
9713 GZ Groningen 
The Netherlands 
Serious Adverse Event Reporting 
QPS SU QPS Clinical Services GmbH  
Parkring 12 Brückenkopfgasse 1, Top 4 und Top 5 
8074 Grambach 8020 Graz 
Austria 
Section 2 – Signature 
Page for Investigators 
 
QPS Netherlands B.V. 
Synopsis – Inclusion 
Criteria 
8. Fulfilling the 2010 American College of Rheumatology 
(ACR)/European Union League Against Rheumatism (EULAR) 
classification criteria for RA. 
• Treatment with a stable dose of MTX for at least 12 
weeks prior to treatment start and planned to continue 
with MTX during the study; if the MTX dose was 
changed during the 12-week period, such a patient 
may be included in the study based on Investigator 
judgement. 
Synopsis – Exclusion 
Criteria 
12. Having evidence of active tuberculosis (TB) or latent TB at 
Screening as assessed by chest X-ray (RA patients only) and/or 
by QuantiFERON®-test. Applicable for RA patients only: in 
case of rescreening within three months after Screening, 
negative results from the initial chest X-ray and/or 
QuantiFERON®-test performed during Screening do not need 
to be repeated. 

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
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Table 5-2: Visit and 
Assessment Schedule 
– Part 2 
Footnote 4:  
Not to be performed when this assessment was done within 3 
weeks prior to dosing and result is available. In case of 
rescreening within three months after Screening, negative 
results from the initial QuantiFERON® test performed during 
Screening do not need to be repeated. 
Footnote 5: 
If a chest X-ray was performed within the past three weeks prior 
to dosing and documentation is available, it is not necessary to 
repeat the chest X-ray. In case of rescreening within three 
months after Screening, negative results from the initial chest 
X-ray performed during Screening do not need to be 
repeated. 
Section 8.3.4.8 
QuantiFERON® Test 
The QuantiFERON® test will be performed at sScreening to test 
for active tuberculosis (TB) or latent TB unless this assessment 
was done within 3 weeks prior to dosing and results are available. 
Applicable for RA patients only: in case of rescreening within 
three months after Screening, negative results from the initial 
QuantiFERON®-test performed during Screening do not need 
to be repeated. For this test 4 tubes of 1 mL blood each will be 
taken. 
Section 8.3.4.9 Chest 
X-ray (RA Patients 
Only) 
Only for RA patients, a chest X-ray will be taken at sScreening to 
test for active TB or latent TB. If a chest X-ray was performed 
within the past three weeks prior to dosing and documentation is 
available, it is not necessary to repeat the chest X-ray. In case of 
rescreening within three months after Screening, negative 
results from the initial chest X-ray performed during 
Screening do not need to be repeated. 
Table 8-4: Blood 
Volume (Part 2) 
Footnote **: 
Unless this assessment was done within 3 weeks prior to dosing 
and result is available. In case of rescreening within three 
months after Screening, negative results from the initial 
QuantiFERON® test performed during Screening do not need 
to be repeated. 
Section 8.4.1 Inclusion 
Criteria 
8. Fulfilling the 2010 American College of Rheumatology 
(ACR)/European Union League Against Rheumatism (EULAR) 
classification criteria for RA [8]. 
Treatment with a stable dose of MTX for at least 12 weeks prior 
to treatment start and planned to continue with MTX during the 
study; if the MTX dose was changed during the 12-week 
period, such a patient may be included in the study based on 
Investigator judgement. 
Section 8.4.2 
Exclusion Criteria 
12. Having evidence of active tuberculosis (TB) or latent TB at 
Screening as assessed by chest X-ray (RA patients only) and/or 
by QuantiFERON®-test. Applicable for RA patients only: in 
case of rescreening within three months after Screening, 
negative results from the initial chest X-ray and/or 
QuantiFERON®-test performed during Screening do not need 
to be repeated. 
 
 

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
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Amendment 5, dated 06 December2023, original protocol issued 15 September 2022, 
Amendment 1 dated 30 November 2020, Amendment 2 dated 24 February 2023, Amendment 
3 dated 28 July 2023 and Amendment 4 dated 29 August 2023. 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20EC of the European Parliament and the Council of the European Union. 
In this amendment, the Principal Investigator of QPS Netherlands B.V. is updated and 2 
additional clinical sites and Principal Investigators are added. The addition of the new clinical 
sites has resulted in several updates to the protocol to accommodate procedures at these sites. 
Section 
Update 
Header  
29 August 2023 06 December 2023, Amendment 4 Amendment 
5 
Title Page 
Authors 
  
Document status/version Amendment 4 Amendment 5 
Date 29 August 2023 06 December 2023 
Contact Details 
Principal investigators 
 
 
 
CHDR 
Zernikedreef 8 
2333 CL Leiden 
The Netherlands 
 
ICON 
Van Swietenlaan 6 
9728 NZ Groningen 
Clinical facilityfacilities 
CHDR 
Zernikedreef 8 
2333 CL Leiden 
The Netherlands 
ICON 
Van Swietenlaan 6 
9728 NZ Groningen 
The Netherlands 
Clinical laboratory: 
Laboratory – chemistry and haematology 
AKCL LUMC, E2-P 
Albinusdreef 2 
2333 ZA Leiden 
The Netherlands 
LUMC Laboratory – Microbiology 

QPS code: 210463-CS0382 
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Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
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Laboratory – Microbiology, E4-P 
Albinusdreef 2 
2333 ZA Leiden 
The Netherlands 
Chest X-Ray: 
DC klinieken 
Krimkade 20 
2251 KA Voorschoten 
The Netherlands 
PharmacyPharmacies: 
Apotheek LUMC, LO-P30 
Einthovenweg 6 
2333 ZC Leiden 
The Netherlands 
Section 1 – Signature 
Page for Lipum AB 
 
 
Section 2 – Signature 
Page for Investigators 
2. SIGNATURE PAGE FOR INVESTIGATORS 
 
 
QPS Netherlands B.V. 
 
Principal Investigator, CHDR 
 
Principal Investigator, ICON 
Section 4 – List of 
Abbreviations 
DAS28 
Disease activity score 28 
DAS28-CRP DAS28 with CRP 
DAS28-ESR DAS28 with ESR 
hsCRP 
High sensitive C-reactive protein 
RDW-CV 
Red blood cell distribution width 
VAS Visual analogue scale 
Synopsis - Center 
CENTERS 
CHDR, Leiden, The Netherlands 
ICON, Groningen, The Netherlands 
Synopsis - Treatments 
Part 2 
There should be at least 4824 hours between administration of 
SOL- 116 and the preceding methotrexate (MTX) dose and at 
least 4824 hours between administration of SOL-116 and the 
subsequent MTX dose. 

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Synopsis – Summary 
of Study Design 
Eligibility will be assessed during a screening period of up to 2842 
days. 
Synopsis – Inclusion 
Criteria 
3. Normal clinically physical findings, apart from RA specific 
findings (including deviating laboratory values e.g., mild anaemia 
or swollen joints) for RA patients, including pulse rate, blood 
pressure, electrocardiogram (ECG), physical examination, and 
laboratory values (haematological/clinical chemistry) as judged 
by the Investigator. Healthy subjects must be negative for anti- 
cyclic citrullinated peptide (CCP) and have Rheumatoid Factor 
<1.5 ULN at Screening. 
8. • 
Use of oral glucocorticosteroids is allowed if equivalent 
to ≤5 mg/day of prednisolone on a stable dose for a least 4 
weeks prior to dosing (Day 1) and expected to remain on that 
dose level for at least 4 weeks after dosing (Day 1). 
Synopsis – Exclusion 
Criteria 
6. 
Use of any prescription or non-prescription drugs 
(excluding paracetamol, hormonal contraceptives), antacids, 
herbal, and dietary supplements (including St John’s Wort) within 
14 days (or 28 days if the drug is a potential hepatic enzyme 
inducer) or 5 half-lives (whichever is longer) prior to the first dose 
of study drug for healthy subjects and within 4 weeks prior to 
the first dose of study drug for RA patients, unless in the 
opinion of the Investigator the medication will not interfere with 
the study procedures or compromise subject/patient safety. In RA 
patients, MTX and folic acid use are exempted. 
7. 
Aspartate 
aminotransferase 
(AST) 
and 
alanine 
aminotransferase (ALT) ≥ 2.0 times upper limit of normal (ULN); 
alkaline phosphatase and bilirubin ≥ 1.5 times the ULN at 
Screening or on Day -1. At Screening, these assessments may 
be repeated once, at the discretion of the Investigator. 
8. 
Serum creatinine > 1.5 times the ULN or estimated 
glomerular filtration rat (eGFR) <60 at Screening or on Day -1 
(for Part 1 and Part 3). Estimated glomerular filtration rat 
(eGFR) <60 at Screening or on Day -1 (for Part 2). At 
Screening, these assessments may be repeated once, at the 
discretion of the Investigator. 
9. 
Subjects/patients who have experienced surgery within 6 
months of the screening visit that could negatively impact on the 
subject’s/patient’s participation in the opinion of thea Principal 
Investigator or responsible physician. 
10. 
SystolicHigh blood pressure of >140 mmHg or a diastolic 
blood pressure of >90 mmHg, confirmed by a repeat test, at 
Screening or on Day -1, judged as clinically relevant by a 
Principal Investigator or responsible physician. A repeat test 
may be performed. 

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18. 
Positive urine drug screen or alcohol breath test at 
Screening or on Day -1. 
20. 
The subject currently smokes or uses nicotine-containing 
products. Former smokers will be eligible, provided they have not 
smoked for at least 1 month prior to Screening. Positive cotinine 
test results at Screening or on Day -1 are reason for exclusion. 
Such positive test results can be repeated once to exclude 
environmental influence on the subject. 
22. 
Intra-articular or systemic corticosteroid injection and/or 
oral administration within 4 weeks prior to dosing. 
Synopsis – 
Exploratory 
Parameters 
• Inflammatory biomarkers (except BSSL): C-reactive protein 
(CRP), 
erythrocyte 
sedimentation 
rate 
(ESR) 
for 
all 
subjects/patients, and S-calprotectin and high sensitive CRP 
(hsCRP) (only RA patients); 
• Cytokine/chemokine panel (including but not limited to IFNγ, 
IL-1β, IL-6, IL-10, IL-12, IL-18, MCP-1 and TNFα).); 
• Flow cytometry panel (only RA patients); 
• Whole blood stimulation assays (only RA patients). 
Table 5-2: Visit and 
Assessment Schedule 
– Part 2 
Screening Day -28 -42 to Day -2 
Patient Global Health VAS Score on Day -1 
DAS28-CRP and DAS28-ESR on Day -1 
Blood sampling for flow cytometry and whole blood 
stimulation assay on Day 1, Day 2, Day 4 Day 8, Day 21 and 
Day 49 
Additional blood sampling for future exploratory analysis on 
Day 1, Day 8 and Day 21 
Abbreviation: DAS28-CRP, disease activity score 28 with C-
reactive protein; DAS28-ESR, disease activity score 28 with 
erythrocyte sedimentation rate; hsCRP, high sensitive C-
reactive protein; SAE, serious adverse event; VAS, visual 
analogue scale 
Updated footnotes (number in table also updated): 
7. The 28-joint assessment will only be performed on Day -1 
(baseline). 
8. There should be at least 4824 hours between administration of 
SOL-116 and the preceding MTX dose and at least 4824 hours 
between administration of SOL-116 and the subsequent MTX 
dose. 
14. On Day 1 prior to dosing. Based on emerging data, 
collection time points may be updated. 
16. Fasting glucose and lipid status determined at Screening, pre-
dose on Day 1, Day 14 and Day 35. α-tocopherol status 

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determined pre-dose on Day 1, Day 14 and Day 35 only. S-
calprotectin and hsCRP determined prior to dosing and 4 hours 
post-dose on Day 1, on Day 2, on Day 4, on Day 21, on Day 49 
and on Day 90. Subjects should be fasting for at least 4 hours prior 
to blood sampling at Screening, and 10 hours prior to blood 
sampling on Day 1, Day 14 and Day 35. Rheumatoid factor and 
anti-CCP antibodies only at Screening. Urinalysis only at 
Screening, on Day 1, on Day 2, on Day 8, on Day 14, on Day 
21, and on Day 90. At Screening, laboratory assessments may 
be repeated once, at the discretion of the Investigator. 
Table 5-3: Visit and 
Assessment Schedule 
for Repeated Dosing 
Part (every Q4W 
dosing) – Part 3 
Day 86 and 88 (+3) 
Alcohol breath test 
Updated footnote: 
 
11. Fasting glucose determined at Screening only. Lipid status 
determined only at Screening and Day 169 only (10 hours’ fasting 
at both occasions). No pancreatic lipase on Day 92. 
Section 6.1.3 – 
Clinical Experience 
with SOL-116 
(current study) 
To date, Part 1 has been concluded. Five cohorts with 8 healthy 
subjects (male and female) per cohort have been administered 
SOL-116 or placebo (6 active and 2 placebo)., up to 6.075 mg/kg 
single dose. 
In Part 2, the enrolment of rheumatoid arthritis (RA)-patients is 
currently ongoing. Part 3, with multiple dosing is ongoing. 
Section 6.3.2 – 
Selection of Dose in 
Part 2 (RA cohort) 
In Part 1 of the study, doses up to 6.075 mg/kg SOL-116 
resulted in an exposure of 12 800 (µg/mL*h) in healthy 
subjects, with no safety or tolerability issues. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 6.3.2 to 6.3.5 
Section numbering updated. 

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Section 8.1.3 – 
Exploratory 
Endpoints (all parts) 
• Change from baseline in inflammatory biomarkers, i.e. serum C-
reactive protein (CRP), erythrocyte sedimentation rate (ESR) for 
all subjects/patients and S-calprotectin and high sensitive CRP 
(hsCRP) (only RA patients). 
• Change form baseline in other exploratory markers (RA 
patients only), based on flow cytometry panel and whole blood 
stimulation assay. 
Section 8.2 – Overall 
Study Design 
Part 2 
Eligibility will be assessed during a screening period of up to 2842 
days. 
In a cohort of up to 8 RA patients (6 active, 2 placebo will be 
randomized and dosed) (Cohort 7), one of the single doses tested 
in healthy subjects was selected, i.e., 2.025 mg/kg will be tested 
(see Section 6.1.3 and Section 6.3.2). 
There should be at least 4824 hours between administration of 
SOL-116 and the preceding methotrexate (MTX) dose and at least 
4824 hours between administration of SOL-116 and the 
subsequent MTX dose. 
Section 8.3.2.2 – RA 
Medical History, 
DAS28-CRP, and 
DAS28-ESR 
8.3.2.2 RA Medical History, DAS28-CRP, and DAS28-ESR 
(RA Patients Only) 
The disease activity score 28 (DAS28) for RA with CRP 
(DAS28-CRP) and the DAS-28 for ESR (DAS28-ESR) will be 
determined on Day -1 (baseline). 
Section 8.3.2.3 – Prior 
and Concomitant 
Medications 
All relevant medications taken from 2 weeks prior to Screening 
(4 weeks for RA cohort) until end-of-study (EOS) or started 
during the study will be recorded on the Concomitant Medications 
page. 
Section 8.3.3.3 - 
Labeling 
Detailed information will be given in the lab manual. 
Section 8.3.4.1 – 
Adverse Events 
Adverse events will be recorded according to the QPS 
Netherlands B.V.local standard operating procedure (SOP)/Work 
instruction of the clinic. 
Section 8.3.4.2 – Vital 
Signs 
Vital sign assessments will be performed according to the QPS 
Netherlands B.V.local SOP of the clinic and will include 
measurements of supine blood pressure, pulse rate, and temporal 
body temperature. Vital sign measurements will be collected after 
the subject/patient has been resting for 5 minutes in a supine 
position. 
Section 8.3.4.3 – Body 
Weight and Height 
The subject’s/patient’s body weight will be measured using a 
validated balance according to the QPS Netherlands B.V.local 
SOP of the clinic. 
Section 8.3.4.4 – 12-
lead ECG 
Subjects/patients will be in a supine position for 5 minutes prior 
to the measurements. ECGs will be evaluated and classified as 

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normal/abnormal according to the QPS Netherlands B.V.local 
SOP of the clinic. 
HR, PR, QRS, and QT will be provided on the print-out of the 
ECG apparatus. or in the electronic Muse system (RA patients 
only). Bazett (QT/RR1/2)/Fridericia (QT/RR1/3) QTc is 
automatically calculated by the ECG apparatus and provided on 
the print-out. or in Muse (RA patients only). 
Evaluation of average recordings will be performed according to 
QPS Netherlands B.V.the local SOP of the clinic. 
Section 8.3.4.5 – 
Physical Examination 
Physical examination will be performed consisting of inspection, 
percussion, palpation, and auscultation according to the QPS 
Netherlands B.V. SOP.local SOP of the clinic. For Part 2, this 
will also (at baseline) include a 28-joint status (number of 
swollen joints and number of tender joints). 
Section 8.3.4.6 – 
Patient Global Health 
VAS Score (Part 2 
Only) 
Section added. 
In Part 2, the patients will be asked (at baseline) to fill in a 
Patient Global Health VAS score. 
Section 8.3.4.7 – 3-
lead ECG (Telemetry) 
Telemetry monitoring will be set on alarm and used for evaluation 
of any cardiac event. It will be performed according to the QPS 
Netherlands B.V.local SOP of the clinic. 
Section 8.3.4.11 – 
Laboratory 
Assessments 
At Screening, laboratory assessments may be repeated once, 
at the discretion of the Investigator. 
As a rule, the blood samples will be taken from the subject/patient 
by puncture of a vein in the cubital or the antebrachial region. 
Table 8-1: Summary 
of Clinical Laboraty 
Tests 
Hematology:  
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Erytoblasts 
Red blood cell distribution width (RDW-CV) 
Chemistry: 
hsCRP (Part 2 only) 
Pancreatic lipasej 
Urinalysis: 
Albumin or micro albumin 
Others: 
Cytokine/chemokine panel (including but not limited to IFNγ, IL
1β, IL 6, IL 10, IL 12, IL 18, MCP 1, and TNFα) 
Footnotes: 
a. Only if urine dipstick is positive and marked as at least ‘++’ for 
blood or protein. 
a. If there is an abnormality in urine in accordance with the 
clinical laboratory standard procedures. 

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i. Only applicable for Part 2. 
j. Not on Day 92 of Part 3 
Section 8.3.4.12 – 
Drug and Cotinine 
Screen 
For a urine drug screening, the following compounds willmay be 
assessed: amphetamine, barbiturates, benzodiazepines, cocaine, 
marijuana 
(THC), 
MDMA/ecstasy, 
methadone, 
methamphetamine, morphine, opioids, phencyclidine, and 
tricyclic antidepressants. 
Section 8.3.4.13 – 
Alcohol Breath Test 
8.3.4.128.3.4.13 Alcohol Breath Test 
TheAn alcohol test (breath test or urine) will be performed 
according to QPS Netherlands B.V.the local SOP of the clinic. 
Section 8.3.4.16 – 
SARS-CoV-2 Test 
COVID-19 testing will be performed according to QPS 
Netherlands B.V. SOP at the time point described in Table 5 1. 
Section 8.3.5 - 
Immunogenicity 
Information on equipment and further details on the procedures 
on the sampling are documented in a separate instruction manual. 
Section 8.3.6 – 
Exploratory 
Asessments 
Blood samples will be taken to check BSSL concentration, 
inflammatory biomarkers, and 
cytokine/chemokine panel 
(including but not limited to IFNγ, IL-1β, IL-6, IL-10, IL-12, 
IL-18, MCP-1, and TNFα), flow cytometry panel (only RA 
patients), and whole blood stimulation (only RA patients) at 
the time points specified in Table 5 1, Table 5 2 and Table 5 3. 
About 4.02.0 mL or 4 mL (2 mL for Part 3 and 4 mL for Parts 
1 and 2) blood for the BSSL samples, and about 2 mL for the 
cytokine/chemokine panel samples will be collected via vena 
puncture or via an IV catheter placed in a vein in the arm 
following the local standard procedures. Information on 
equipment and further details on the procedures on the sampling 
are documented in a separate instruction manualIn Part 2, about 
10 mL for the flow cytometry panel and about 10 mL for the 
whole blood stimulation assay will be collected. 
Section 8.3.6.1 - 
Exploratory Samples 
(Future Analysis) 
At time points specified in Table 5 1, Table 5 2 and Table 5 3, an 
extra blood samplesamples (5.5 mL in total) will be taken for 
future exploratory analysis of potential PK and/or PD markers of 
relevance for SOL-116. 
Section 8.3.7 – Order 
of Assessments 
In case several study procedures are scheduled at the same time 
point, the following sequence should be followed pre-dose: 12-
lead ECG, vital signs, asking for AEs, PK blood sampling, blood 
sampling for immunogenicity, blood sampling for BSSL, blood 
sampling for cytokine and chemokine panel, blood sampling for 
flow cytometry panel (Part 2 only), blood sampling for whole 
blood stimulation assay (Part 2 only), blood sampling for 
future exploratory analysis, and blood sampling for clinical 
laboratory tests. Post-dose, the following sequence should be 
followed: 
PK 
blood 
sampling, 
blood 
sampling 
for 
immunogenicity, blood sampling for BSSL, blood sampling for 
cytokine and chemokine panel, blood sampling for flow 
cytometry panel (Part 2 only), blood sampling for whole blood 
stimulation assay (Part 2 only), blood sampling for future 

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the first dose of study drug for RA patients, unless in the 
opinion of the Investigator the medication will not interfere with 
the study procedures or compromise subject/patient safety. In RA 
patients, MTX and folic acid use are exempted. 
7. 
Aspartate 
aminotransferase 
(AST) 
and 
alanine 
aminotransferase (ALT) ≥ 2.0 times upper limit of normal (ULN); 
alkaline phosphatase and bilirubin ≥ 1.5 times the ULN at 
Screening or on Day -1. At Screening, these assessments may 
be repeated once, at the discretion of the Investigator. 
8. 
Serum creatinine > 1.5 times the ULN or estimated 
glomerular filtration rat (eGFR) <60 at Screening or on Day -1 
(for Part 1 and Part 3). Estimated glomerular filtration rat 
(eGFR) <60 at Screening or on Day -1 (for Part 2). At 
Screening, these assessments may be repeated once, at the 
discretion of the Investigator. 
9. 
Subjects/patients who have experienced surgery within 6 
months of the screening visit that could negatively impact on the 
subject’s/patient’s participation in the opinion of thea Principal 
Investigator or responsible physician. 
10. 
SystolicHigh blood pressure of >140 mmHg or a diastolic 
blood pressure of >90 mmHg, confirmed by a repeat test, at 
Screening or on Day -1, judged as clinically relevant by a 
Principal Investigator or responsible physician. A repeat test 
may be performed. 
18. 
Positive urine drug screen or alcohol breath test at 
Screening or on Day -1. 
20. 
The subject currently smokes or uses nicotine-containing 
products. Former smokers will be eligible, provided they have not 
smoked for at least 1 month prior to Screening. Positive cotinine 
test results at Screening or on Day -1 are reason for exclusion. 
Such positive test results can be repeated once to exclude 
environmental influence on the subject. 
22. 
Intra-articular or systemic corticosteroid injection and/or 
oral administration within 4 weeks prior to dosing. 
Section 8.4.3.1 – 
Concomitant 
Medication 
From 2 weeks (or 28 days if the drug is a potential hepatic enzyme 
inducer) or 5 half-lives (whichever is longer) prior to Screening 
(or 4 weeks for RA cohort) until the EOS, prescribed or over-
the-counter medication (including herbal remedies) is only 
allowed as described in exclusion criterion 6. 
If there is a medical need, local intra-articular corticosteroid 
injections are permitted at the discretion of thea Principal 
Investigator. 
The patients in the RA cohort will be treated with MTX. There 
should be at least 4824 hours between administration of SOL-116 

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and the preceding MTX dose and at least 4824 hours between 
administration of SOL-116 and the subsequent MTX dose. 
Section 8.5.2 – Study 
Drug Preparation 
All study drugs will be prepared (packaged and labeled in 
individual doses) at QPS Netherlands B.V. (for Part 1 and Part 
3) or the pharmacy of the Leiden University Medical Center 
(LUMC) (for Part 2) by an unblinded pharmacist, or his/her 
designee. 
Section 8.5.5 – Study 
Drug Administration 
In Part 2, there should be at least 4824 hours between 
administration of SOL-116 and the preceding MTX dose and at 
least 4824 hours between administration of SOL-116 and the 
subsequent MTX dose. 
Section 8.6 – Safety 
Review Committee 
• Principal Investigator(s) or delegate(s) (delegation only when 
thea Principal Investigator is not available); 
Section 8.7.1 – 
Determination of Dose 
Escalation/Subsequent 
Dosing 
For PartsPart 1 and 2: The decision to escalate to the next dose 
level will not take place until the SRC has reviewed the blinded 
safety and tolerability data, including but not limited to vital signs, 
ECG results, clinical laboratory tests, and AEs, up to and 
including 14 days post-dose of at least 6 evaluable subjects 
(subject assessed as pharmacokinetically evaluable at Day 14). 
For Part 2: The same applies as for Part 1 but will include 21 
days data for safety/PK review. 
The SRC, Principal Investigator(s) or Lipum AB may terminate 
dose escalation at any time if continuing to a higher dose level 
would jeopardize the safety of the subjects/patients. 
Section 8.10.2 – 
Treatment 
Assignment 
Individual sealed randomization codes are kept by QPS 
Netherlands B.V.,at the participating sites, and these are used 
for emergency un-blinding only. 
Section 8.10.3 – 
Double-blinding 
Therefore, the bioanalytical laboratory will receive the 
randomization list from the pharmacybiostatistician. 
Section 8.11.4 – 
Exploratory 
Parameters 
• Inflammatory biomarkers (except BSSL): CRP, ESR for all 
subjects/patients, and S-calprotectin and hsCRP (only RA 
patients); 
• Cytokine/chemokine panel (including but not limited to IFNγ, 
IL-1β, IL-6, IL-10, IL-12, IL-18, MCP-1 and TNFα).); 
• Flow cytometry panel (only RA patients); 
• Whole blood stimulation assays (only RA patients). 
Section 9.2.2.4 – 
Reporting Procedures 
All SAEs must be reported by thea Principal Investigator to QPS 
SU within 24 hours of the Investigator'sInvestigator’s knowledge 
of the event. 
Section 10.9 – Interim 
Safety Report 
Based on the results of the interim analysis (including but not 
limited to AEs, vital signs, ECGs, and clinical laboratory tests), a 
decision will be taken by the Principal Investigator(s) and Lipum 
AB whether the next cohort can start with the planned dose. This 
decision will only be made after discussion between the Principal 
Investigator(s) and the Sponsor and after mutual agreement and 

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must be submitted to the IEC/IRB for approval before dosing can 
proceed. 
Section 10.10 – 
Clinical Study Report 
Safety and tolerability parameters as well as PK and exploratory 
parameters (BSSL, CRP, hsCRP, ESR and S-calprotectin) will be 
evaluated in a Clinical Study Report. 
Section 12.1.1 – 
Protocol Amendments 
It should be reviewed by the Principal Investigator(s), Sponsor 
and other relevant team members, if appropriate. 
Section 12.1.3.1 – Data 
Collection 
Data will be collected using paper source, and via eSource. 
Inaccording to local SOP of the clinic. the Data Management 
Plan, a specification will be made for which assessments the data 
will be collected via eSource. 
For each randomized subject/patient, regardless of study drug 
initiation, an eCRF must be completed and signed by thea 
Principal Investigator or sub-investigator. 
Section 12.1.3.2 – Data 
Management and 
Quality Control 
The CRA will use the eCRF systems (OpenClinica and 
ClinSpark) to track the monitoring queries and their resolution by 
the site. 
Section 13 Structured 
Risk Analysis 
A risk analysis (TSP603.02) will be made by the Division Clinical 
of QPS Netherlands B.V. 
New section added. 
 
 
 

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Amendment 4, dated 29 August 2023, original protocol issued 15 September 2022, 
Amendment 1 dated 30 November 2020, Amendment 2 dated 24 February 2023 and 
Amendment 3 dated 28 July 2023. Amendment 4 is identical to Amendment 3 plus that EC’s 
comments were incorporated and minor corrections done. 
Section 
Update 
Header  
28 July 2023 29 August 2023, Amendment 3 Amendment 4 
Title Page 
Document status/version Amendment 3 Amendment 4 
Date 28 July 2023 29 August 2023 
Table 5-2: Visit 
and Assessment 
Schedules 
Footnote 14 was updated: “CRP, ESR and S-calprotectin determined 
prior to dosing and 4 hours post-dose on Day 1, on Day 2, on Day 4, 
on Day 49 and on Day 90.” 
The rest of the footnote remains the same. The update was done to 
correct a prior mistake. 
Table 5-3: Visit 
and Assessment 
Schedule for 
Repeated Dosing 
Part (every Q4W 
dosing) – Part 3 
 
BMI was added. 
The update was done to correct a prior mistake. 
Table 8-6: 
Assignment of 
Study Codes to 
Subjects/Patients 
The clarification: “Healthy subjects” was added 
 

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Amendment 3, dated 28 July 2023, original protocol issued 15 September 2022, Amendment 
1 dated 30 November 2020 and Amendment 2 dated 24 February 2023. 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20EC of the European Parliament and the Council of the European Union. 
In this amendment, updates were made to study design including addition of a multiple dosing 
part (Part 3), updates of inclusion and exclusion criteria, involved laboratories have been 
defined, Sponsor’s Chief Medical Officer was updated and administrative updates. 
Section 
Update 
Header  
24 February 2023 28 July 2023, Amendment 2 Amendment 3 
Title Page 
Document status/version Amendment 2 Amendment 3 
Date 24 February 2023 28 July 2023 
Contact Details 
BSSL ANALYSES: 
BioAgilytix Europe GmbHPelago Biosciences 
Lademannbogen 10, 22339 Hamburg 
Germany 
Scheeles väg 1 
SE 171 65 Solna 
Sweden 
 
CYTOKINE ANALYSES: 
TATAA Biocenter AB 
Sofierogatan 3A 
SE-412 51 Gothenburg, Sweden 
Signature Page 
for Lipum AB 
 
Chief Medical Officer 
Synopsis - 
Objectives 
Objectives for single dosing (Parts 1 and 2) 
 
Primary objective: 
• To evaluate the safety and tolerability of single ascending doses of 
SOL-116 in healthy subjects and rheumatoid arthritis (RA) patients. 
Secondary objective: 
• To determine single dose pharmacokinetic (PK) characteristics of 
SOL-116 in healthy subjects and RA patients. 
• To assess the immunogenicity of SOL-116 after single SC doses in 
healthy subjects and RA patients.  
Exploratory objectives: 
• To 
evaluate 
the 
effect 
of 
single 
ascending 
doses 
of  
SOL-116 on bile salt-stimulated lipase (BSSL) concentration in the 
blood of healthy subjects and RA patients. 
• To evaluate the pharmacodynamic (PD) effect of single ascending 
doses of SOL-116 on inflammatory biomarkers in the blood of healthy 
subjects and RA patients. 

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Objectives for multiple dosing (Part 3) 
Primary objective: 
• To evaluate the safety and tolerability of multiple dosing of SOL-
116 in healthy subjects. 
Secondary objective: 
• To determine multiple dose PK characteristics of SOL-116 in 
healthy subjects. 
• To assess the immunogenicity of SOL-116 after multiple SC doses 
in healthy subjects. 
Exploratory objectives: 
• To evaluate the effect of multiple doses of SOL-116 on BSSL 
concentration in the blood of healthy subjects.  
• To evaluate the PD effect of multiple doses of SOL-116 on 
inflammatory biomarkers in the blood of healthy subjects. 
Synopsis - 
Treatments 
Part 3 
Up to two multiple dosing cohorts of 8 healthy subjects (6 active, 2 
placebo) (Cohorts MD1 and MD2) are planned, i.e. in total up to 16 
subjects will be randomized and dosed.  
The starting dose in Cohort MD1 will be 3.0 mg/kg SOL-116 given as 
SC injection(s). 
 
 
 
 
  
Sentinel dosing will be employed in all cohorts. Thus, within each 
cohort initially 1 subject will receive SOL-116 and 1 subject will 
receive placebo. The remaining 6 subjects of the cohort may be dosed 
at least 48 hours after dosing of the initial 2 subjects of the cohort, 
provided no clinically significant safety issues, as judged by the 
Investigator, are noted in the 48 hours after dosing of the initial 2 
subjects of the cohort. 
After each cohort completes dosing, a dose escalation SRC meeting 
will take place. Escalation to the next MD dose cohort may occur only 
after evaluation of the safety/tolerability and available PK data up to 
and including 28 days post last dose of at least 6 evaluable subjects 
(subject assessed as pharmacokinetically evaluable at Day 28) and 
after approval by the IEC. This time point may be adjusted based on 
the PK data of previous cohorts if the SRC recommends. 
Synopsis – 
Summary of 
Study Design 
Eligibility will be assessed during a screening period of up to 28 days. For 
the treatment period, subjects/patients will check into the clinic one day 
prior to dosing (Day -1). On Day 1, all subjects/patients will receive SOL-
116 in a fasted state (after an overnight fast of at least 10 hours). 
Subjects/patients will be released from the clinic on Day 4 (Part 1) or Day 

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2 (Part 2), after all required study procedures are completed and if 
medically justified. If medically indicated and/or based on emerging data, 
patients in Part 2 may be asked to return on Day 3 for additional safety 
assessments (optional visit). Furthermore, in both parts the clinic stay may 
be extended up to Day 7 if medically indicated and/or based on emerging 
data. In total, subjects/patients will return to the clinic for 6 (Part 1) or up 
to 8 (Part 2) ambulant visits up to Day 63. Subjects/patients will return to 
the clinic on Day 90 for an EOS/follow-up visit. 
A multiple dosing part will be performed in healthy subjects where, 
in the first multiple dosing cohort, each subject will receive a total of 
four doses every fourth week (Q4W): at baseline (D1) and Days 29, 
57 and 85. With a dose interval of 28 days, it is estimated that with 
the half-life of SOL-116 (assessed in the SAD) concentrations at, or 
close to, steady state will be reached after the fourth dose. The 
subjects are followed up until Day 169. 
Synopsis – Study 
Population 
Up to 48 healthy male or female subjects and 8 male or female RA patients 
(for Parts 1 and 2, respectively). Preferably at least 3 out of 8 subjects 
per cohort should be of the least represented sex (female or male), 
respectively. The study also includes up to 16 healthy adult subjects in 
one or two multiple dosing cohorts (Part 3). 
Synopsis – 
Inclusion 
Criteria 
2. Males and females aged between 18 and 65 years (inclusive) at 
Screening. For patients in the RA cohort, an age interval between 18 
and 70 years (inclusive). 
 
3. Normal clinically physical findings, apart from RA specific findings 
(including deviating laboratory values e.g., mild anaemia) for RA 
patients, including pulse rate, blood pressure, electrocardiogram (ECG), 
physical examination, and laboratory values (haematological/clinical 
chemistry) as judged by the Investigator. Healthy subjects must be 
negative for anti- cyclic citrullinated peptide (CCP) and have Rheumatoid 
Factor <1.5 ULN at Screening. 
 
4. For Parts 1 and 3, bBody mass index (BMI) between 19.0 and 30.0 
kg/m2 and body weight between 50 to 100 kg (inclusive) at Screening. 
For Part 2, body weight between 50 to 120 kg (inclusive) at Screening. 
 
5. Sexually active male patients participating in the study must use a 
barrier method of contraception (condom) and refrain from sperm 
donation during the study and for 150 days after last dosing if their female 
sexual partner is of childbearing potential. Acceptable methods of birth 
control for female partners of male subjects are: hormonal contraceptives 
(oral contraceptives, implant or injection), intrauterine device (placed at 
least 1 month before the start of the study). Surgical sterilization of male 
patients can be accepted as a form of birth control if the sterilization 
procedure took place at least 6 months prior to the start of the study. 
8. The following inclusion criterion is only applicable for RA patients: 

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Fulfilling the 2010 American College of Rheumatology (ACR)/European 
Union League Against Rheumatism (EULAR) classification criteria for 
RA. 
• Treatment with a stable dose of MTX for at least 12 weeks prior 
to treatment start and planned to continue with MTX during the 
study. 
• Patients naïve to biological disease modifying anti-rheumatic drug 
(bDMARD) or who are washed out (at least 5 half-lives) from 
such therapy before study drug dosing. 
Synopsis – 
Exclusion 
Criteria 
8. Serum creatinine > 1.5 times the ULN or estimated glomerular filtration 
rat (eGFR) <70 60 at Screening or on Day -1. 
10. Systolic blood pressure of ≥ >140 mmHg or a diastolic blood pressure 
of ≥ >90 mmHg, confirmed by a repeat test, at Screening or on Day -1.  
13. Subjects/patients who are currently enrolled in or have recently 
participated in another interventional clinical study defined as having 
received the last intervention within 90 days or 5 half-lives of the study 
drug (whichever is longer) prior to dosing of the study drug(Parts 1 and 
2) vs. prior to first dosing (Part 3) of the study drug. 
15. Receipt of a vaccine (except COVID 19 vaccine) within 4 weeks 
(COVID-19 vaccine within 6 weeks) prior to dosing and/or the intention 
to receive a vaccine during the study. Deviation from this should be 
judged by the Investigator and in dialogue with the Sponsor. 
16. Recent confirmed COVID-19 infection, with less than 6 weeks 
between recovery and dosing of study drug, and/or receipt of a COVID
19 vaccine within 6 weeks prior to dosing of the study drug or having the 
intention to receive such a vaccine within 7 weeks post dosing of study 
drug. 
20. The subject currently smokes or uses nicotine-containing products. 
Former smokers will be eligible, provided they have not smoked for at 
least 3 1 months prior to Screening. Positive cotinine test results at 
Screening or on Day -1 are reason for exclusion. 
The following exclusion criteria are only applicable for RA patients: 
22. Intra-articular or systemic corticosteroid injection and/or oral 
administration within 4 weeks prior to randomization dosing. 
23. 
Current or expected need of other immunosuppressant medication 
except MTX and/or expected need for intra-articular corticosteroid 
injections. 
Synopsis – 
Pharmacokinetic 
Parameters 
In multiple dosing part, also:  
Minimum observed serum concentration at steady state (Ctrough), time 
to steady state, accumulation ratio. 
Table 5-2: Visit 
and Assessment 
Schedules 
SARS-CoV-2 test taken out 
 

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Table 5-3: Visit 
and Assessment 
Schedules 
Added Table for Part 3 
Section 6.1.3 – 
Clinical 
Experience with 
SOL-116 
(current study) 
6.1.3 Clinical Experience with SOL-116 (current study) 
To date, Part 1 has been concluded. Five cohorts with 8 healthy 
subjects (male and female) per cohort have been administered SOL-
116 or placebo (6 active and 2 placebo). There were 25 males and 15 
females enrolled, age range 22 to 64 years. No subjects dropped out, 
few adverse events and no serious adverse event (SAE) were reported. 
There were no clinically relevant changes from baseline reported on 
the following: vital signs, ECG parameters, telemetry, clinical 
laboratory, physical examination. The serum SOL-116 exposure 
(AUC, Cmax) increased in an approximately dose-proportional 
manner.  
In Part 2, the enrolment of rheumatoid arthritis (RA)-patients is 
currently ongoing. 
Section 6.2.1 – 
Rationale for 
Study Design 
In the multiple dosing part in healthy subjects, up to two multiple 
dosing cohorts (6:2) will be conducted sequentially, but with an 
overlap, where the 28-day (i.e., Tmax plus one half-life) safety and PK 
data post last dose will be assessed by a Safety Review Committee 
(SRC). The SRC will decide if, and at what dose level, the subsequent 
cohort may commence. For the first multiple dosing cohort (MD1), 
the dose and dose interval will be based on all available SAD data and 
PK modelling data. The subjects will be followed for approximately 
90 days post-treatment in order to get an estimate of clearance and 
elimination half-life after multiple dosing. 
Section 6.3.1 – 
Selection of 
Staring dose in 
Part 1 SAD 
Header updated 
Section 6.3.2 – 
Maximum 
Exposure (SAD) 
Header updated 
Section 6.3.3 – 
Selection 
of 
Starting 
Dose 
and 
Dose 
Interval 
in 
Multiple Dosing 
Cohort(s) 
6.3.3 Selection of Starting Dose and Dose Interval in Multiple Dosing 
Cohort(s) 
The starting dose in the first multiple dosing cohort (MD1) will be 3.0 
mg/kg. This dose level is predicted to result in an exposure within the 
same order of magnitude as the expected therapeutic concentration 
in humans. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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The subjects will be administered study drug approximately every 
four weeks for 12 weeks (total of 4 doses). This administration 
schedule was selected for the first multiple dosing cohort from the 
projected time to reach steady state, which is based on the half-life of 
SOL-116 observed in Part 1 of this study (approximately 19 days).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 6.3.4 – 
Maximum 
Exposure 
(Multiple Dosing 
Part) 
6.3.4 Maximum Exposure (Multiple Dosing Part) 
 
 
 
 
Section 7.1 – 
Study Objectives 
for Single Dosing 
(Parts 1 and 2) 
Header updated 
Section 7.2 – 
Study Objectives 
for Multiple 
Dosing (Part 3) 
Primary objective: 
• To evaluate the safety and tolerability of multiple dosing of 
SOL-116 in healthy subjects. 
Secondary objective: 
• To determine multiple dose PK characteristics of SOL-116 in 
healthy subjects. 
• To assess the immunogenicity of SOL-116 after multiple SC 
doses in healthy subjects. 

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Exploratory objectives: 
• To evaluate the effect of multiple doses of SOL-116 on BSSL 
concentration in the blood of healthy subjects.  
• To evaluate the PD effect of multiple doses of SOL-116 on 
inflammatory biomarkers in the blood of healthy subjects. 
Section 8.1.1 – 
Primary 
Endpoints 
Header updated 
Section 8.1.2.1 – 
Secondary 
Endpoints 
• PK of SOL-116 variables for single dose regimens: area under the 
serum concentration-time from time zero to infinity (AUC0-inf), 
AUC from time zero to time t of the last measured concentration 
above the limit of quantification (AUC0-t), area under the serum 
concentration-time from time zero to the end of dosing interval 
(AUC0-tau) (Part 3), maximum observed serum concentration 
(Cmax), time to Cmax (Tmax), terminal elimination half-life (T1/2) 
(Parts 1 and 2), apparent volume of distribution (Vz/F) (Parts 1 
and 2), apparent total body clearance (CL/F) (Parts 1 and 2) and 
dose proportionality after single dose (based on AUC and Cmax) 
(Part 1). 
Section 8.1.2.2 – 
Secondary 
Endpoints Part 3 
only 
PK of SOL-116 variables for the last dose: area under the serum 
concentration-time from time zero to the end of dosing interval 
(AUC0-tau), maximum observed serum concentration (Cmax), time to 
Cmax (Tmax), minimum observed serum concentration (Ctrough), 
average serum concentration (Cave), apparent total body clearance 
at steady state (CLss/F), time to steady state, accumulation ratio in 
Cmax and AUC0-tau. 
Section 8.1.3 
Header updated 
Section 8.2 – 
Overall Study 
Design 
This is a randomized, double-blind, placebo-controlled phase I, first-
in-human (FIH) study designed to evaluate the safety, tolerability and 
PK of single SC ascending doses of SOL-116 in healthy subjects and 
adult RA patients (Parts 1 and 2) and multiple SC doses in healthy 
subjects (Part 3). 
Part 3 
The multiple dosing part will be in healthy subjects where, in the first 
multiple dosing cohort, each subject will receive a total of four doses 
every fourth week (Q4W): at baseline (D1) and Days 29, 57 and 85. 
With a dose interval of 28 days, it is estimated that with the half-life 
of SOL-116 (assessed in the SAD) concentrations at, or close to, steady 
state will be reached after the fourth dose. 
Eligibility will be assessed during a screening period of up to 28 days. 
For the first dose, subjects will check into the clinic one day prior to 
dosing (Day -1). On Day 1, all subjects will receive SOL-116 or 
placebo. Subjects will be released from the clinic on Day 2, after all 
required study procedures are completed and if medically justified. 
If medically indicated and/or based on emerging data, the clinic stay 

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may be extended up to Day 7. Subjects will return to the clinic for 15 
ambulant visits up to Day 154. Subjects will return to the clinic on 
Day 169 for an EOS/follow-up visit. After the second and third dose, 
a phone contact will be made (3 to 7 days after the dose) with the 
subject to ensure no new adverse events or if new medication has been 
added. 
Up to two multiple dosing cohorts of 8 healthy subjects (6 active, 2 
placebo) (Cohorts MD1 and MD2) are planned, i.e. in total up to 16 
subjects will be randomized and dosed.  
The starting dose in Cohort MD1 will be 3.0 mg/kg SOL-116 given as 
SC injection(s) (see Section 6.3.3). 
 
 
 
 
.  
Sentinel dosing will be employed in all cohorts. Thus, within each 
cohort initially 1 subject will receive SOL-116 and 1 subject will 
receive placebo. The remaining 6 subjects of the cohort may be dosed 
at least 48 hours after dosing of the initial 2 subjects of the cohort, 
provided no clinically significant safety issues, as judged by the 
Investigator, are noted in the 48 hours after dosing of the initial 2 
subjects of the cohort. 
After each cohort completes dosing, a dose escalation SRC meeting 
will take place (see Section 8.7.1). Escalation to the next MD dose 
cohort may occur only after evaluation of the safety/tolerability and 
available PK data up to and including 28 days post last dose of at least 
6 evaluable subjects (subject assessed as pharmacokinetically 
evaluable at Day 28) and after approval by the IEC. This time point 
may be adjusted based on the PK data of previous cohorts if the SRC 
recommends. 
Please refer to Table 5-3 for an overview of ambulatory visits and 
residence in the clinic. 
Section 8.3.3.1 – 
Timing for 
Sampling 
Table 5-1,  and Table 5-2 and Table 5-3 provide an overview of all PK 
blood sampling time points. 
Section 8.3.4 – 
Safety and 
Tolerability 
Assessments 
Table 5-1,  and Table 5-2 and Table 5-3 provide an overview of all time 
points on which safety assessments will be performed. 
Section 8.3.4.10 – 
Laboratory 
Assessments 
For Part 1 and 2, tThe blood samples will be taken under fasted 
conditions at time points specified in Table 5-1 and Table 5-2 (due to 
fasting glucose and/or lipid and α-tocopherol status). On these days, 
subjects/patients will not be allowed to eat or drink (except water) for a 
period of 4 hours (Screening) or 10 hours (other time points as specified 
in Table 5-1 and Table 5-2) prior to blood sampling. For Part 3, fasting 
glucose will be determined at Screening only. Moreover, lipid status 

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will be determined only at Screening and Day 169 (10 hours’ fasting 
at both occasions), see Table 5-3.   
Table 8-1 – 
Summary of 
Clinical 
Laboratory Tests 
f. 
Only at Screening, pre-dose on Day 1, Day 14 and Day 35 (Parts 
1 and 2). For Part 3 at Screening and Day 169 (EOS). 
g. 
A SARS-CoV-2 rapid test will be performed on Day -1 (Part 1 
only). At the discretion of the Investigator, a SARS-CoV-2 PCR or rapid 
test may be performed at other time points during the study. 
h. 
Only pre-dose on Day 1, Day 14 and Day 35 (Parts 1 and 2). For 
Part 3 at Screening and Day 169 (EOS). 
Section 8.3.4.13 – 
Pregnancy Test 
A serum pregnancy test will be performed at Screening. A urine pregnancy 
test will be performed on Day -1, Visit 7 (Parts 1 and 3), Visit 8 (Part 3) 
or and Visit 9 (Parts 2 and 3) and at the EOS examination (or at early 
termination) (all parts). The results must be available prior to dosing. 
Section 8.3.4.15 – 
SARS-CoV-2 
Test 
COVID-19 testing will be performed according to QPS Netherlands B.V. 
SOP at the time point described in Table 5-1and Table 5 2. A check on 
health status will be performed and body temperature will be measured 
before the subject/patient enters the clinic on Day -1 (Part 1). For Parts 
2 and 3, COVID-19 testing is not mandatory as recommendations 
have changed since the study started. Testing for COVID-19 will be 
done at the discretion of the investigator, based on clinical symptoms. 
Section 8.3.5 - 
Immunogenicity 
Blood samples will be taken to check for the presence of ADA at time 
points specified in Table 5-1,  and Table 5-2 and Table 5-3. 
Section 8.3.5 – 
Exploratory 
Assessments 
Blood samples will be taken to check BSSL concentration, inflammatory 
biomarkers, and cytokine/chemokine panel at the time points specified in 
Table 5-1,  and Table 5-2 and Table 5-3. 
Section 8.3.6.1 – 
Exploratory 
Samples (Future 
Analysis) 
At time points specified in Table 5-1,  and Table 5-2 and Table 5-3, an 
extra blood sample (5.5 mL) will be taken for future exploratory analysis 
of potential PK and/or PD markers of relevance for SOL-116. The 
samples will be discarded at the latest 10 years after the sampling 
occasion. 
Section 8.3.9 – 
Total Blood 
Volume 
Table 8-5: Blood Volume (Part 3): Added due to a Part 3 added 
Section 8.4 – 
Study Population 
The subject population will include healthy adult subjects (Cohort 1-6 of 
Part 1 and multiple dosing cohorts of Part 3) and patients (Cohort 7, 
Part 2) who satisfy all entry criteria.  
Section 8.4.1 – 
Inclusion criteria 
2. Males and females aged between 18 and 65 years (inclusive) at 
Screening. For patients in the RA cohort, an age interval between 18 
and 70 years (inclusive). 
 
3. Normal clinically physical findings, apart from RA specific findings 
(including deviating laboratory values e.g., mild anaemia) for RA 
patients, including pulse rate, blood pressure, electrocardiogram (ECG), 
physical examination, and laboratory values (haematological/clinical 

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chemistry) as judged by the Investigator. Healthy subjects must be 
negative for anti- cyclic citrullinated peptide (CCP) and have Rheumatoid 
Factor <1.5 ULN at Screening. 
 
4. For Parts 1 and 3, bBody mass index (BMI) between 19.0 and 30.0 
kg/m2 and body weight between 50 to 100 kg (inclusive) at Screening. 
For Part 2, body weight between 50 to 120 kg (inclusive) at Screening. 
 
5. Sexually active male patients participating in the study must use a 
barrier method of contraception (condom) and refrain from sperm 
donation during the study and for 150 days after last dosing if their female 
sexual partner is of childbearing potential. Acceptable methods of birth 
control for female partners of male subjects are: hormonal contraceptives 
(oral contraceptives, implant or injection), intrauterine device (placed at 
least 1 month before the start of the study). Surgical sterilization of male 
patients can be accepted as a form of birth control if the sterilization 
procedure took place at least 6 months prior to the start of the study. 
8. The following inclusion criterion is only applicable for RA patients: 
Fulfilling the 2010 American College of Rheumatology (ACR)/European 
Union League Against Rheumatism (EULAR) classification criteria for 
RA. 
• Treatment with a stable dose of MTX for at least 12 weeks prior 
to treatment start and planned to continue with MTX during the 
study. 
Patients naïve to biological disease modifying anti-rheumatic drug 
(bDMARD) or who are washed out (at least 5 half-lives) from such 
therapy before study drug dosing. 
Section 8.4.2 – 
Exclusion 
criteria 
8. Serum creatinine > 1.5 times the ULN or estimated glomerular filtration 
rat (eGFR) <70 60 at Screening or on Day -1. 
10. Systolic blood pressure of ≥ >140 mmHg or a diastolic blood pressure 
of ≥ >90 mmHg, confirmed by a repeat test, at Screening or on Day -1. 
For   
13. Subjects/patients who are currently enrolled in or have recently 
participated in another interventional clinical study defined as having 
received the last intervention within 90 days or 5 half-lives of the study 
drug (whichever is longer) prior to dosing of the study drug(Parts 1 and 
2) vs. prior to first dosing (Part 3) of the study drug. 
15. Receipt of a vaccine (except COVID 19 vaccine) within 4 weeks 
(COVID-19 vaccine within 6 weeks) prior to dosing and/or the intention 
to receive a vaccine during the study. Deviation from this should be 
judged by the Investigator and in dialogue with the Sponsor. 
16. Recent confirmed COVID-19 infection, with less than 6 weeks 
between recovery and dosing of study drug, and/or receipt of a COVID
19 vaccine within 6 weeks prior to dosing of the study drug or having the 
intention to receive such a vaccine within 7 weeks post dosing of study 
drug. 

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20. The subject currently smokes or uses nicotine-containing products. 
Former smokers will be eligible, provided they have not smoked for at 
least 3 1 months prior to Screening. Positive cotinine test results at 
Screening or on Day -1 are reason for exclusion. 
The following exclusion criteria are only applicable for RA patients: 
22. Intra-articular or systemic corticosteroid injection and/or oral 
administration within 4 weeks prior to randomization dosing. 
24. 
Current or expected need of other immunosuppressant medication 
except MTX and/or expected need for intra-articular corticosteroid 
injections. 
 
Section 8.4.3.1 – 
Concomitant 
Medication 
From 2 weeks (or 28 days if the drug is a potential hepatic enzyme 
inducer) or 5 half-lives (whichever is longer) prior to Screening until the 
EOS prescribed or over-the-counter medication (including herbal 
remedies) is not allowed, except for medication that is required for the 
treatment of AEs is only allowed as described in exclusion criterion 6. 
Any new concomitant medication for treatment of AEs should 
preferably be discussed beforehand with the Investigator. The 
occasional use of paracetamol is allowed. Female subjects/patients are 
allowed to use oral contraception, a hormonal implant or hormonal intra-
uterine devices as contraception. Oral corticosteroids are not allowed 
during study. RA patients only (Part 2): If there is a medical need, local 
intra-articular corticosteroid injections are permitted at the discretion of 
the Principal Investigator.  
Part 3 only: Medications for incidental use (e.g., hay fever) may, at 
the Investigator’s discretion, be allowed during the study. 
Section 8.4.3.2 – 
COVID-19 
Section was removed 
Section 8.4.3.2 - 
Alcohol 
Drinking of alcoholic beverages is not permitted from 48 hours prior to 
each clinic visit or stay  or while in the clinic until clinic discharge.  
Section 8.4.3.3 – 
Physical 
Activities 
From Screening until the Day 14 visit as well as 48 24 hours prior to each 
clinic visit thereafter, the subjects/patients should refrain from excessive 
physical exercise and strenuous sports activities (endurance sports). 
Section 8.4.3.4 – 
Dietary Aspects 
Consumption of food containing poppy seeds is not allowed from 24 hours 
prior to Screening and prior to Day -1. 
Section 8.4.3.5 - 
Smoking 
Smoking is not permitted from three one months prior to Screening up to 
and including the EOS visit. 
Section 8.4.3.6 
Participation in 
Other Clinical 
Studies 
Study subjects are not allowed to participate in any other interventional 
clinical drug study during the study period. 
Section 8.5.5 – 
Study Drug 
Administration 
In Part 3, the same applies but 4 dose administrations (with maximum 
4 injections per occasion) will be administered with 28 days’ interval 
(in MD1). 

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Section 8.6 – 
Safety Review 
Committee 
For Part 3, the same applies but data up to 28 days post last dose will 
be collected and assessed at the SRC. 
Section 8.7.1 – 
Determination of 
Dose 
Escalation/Subse
quent Dosing 
For Parts 1 and 2: The decision to escalate to the next dose level will not 
take place until the SRC has reviewed the blinded safety and tolerability 
data, including but not limited to vital signs, ECG results, clinical 
laboratory tests, and AEs, up to and including 14 days post-dose of at least 
6 evaluable subjects (subject assessed as pharmacokinetically evaluable 
at Day 14). 
For Part 3: The decision to escalate to the next dose level will not take 
place until the SRC has reviewed the blinded safety and tolerability 
data, including but not limited to vital signs, ECG results, clinical 
laboratory tests, and AEs, up to and including 28 days (i.e., Tmax plus 
one half-life) post last dose of at least 6 evaluable subjects (subject 
assessed as pharmacokinetically evaluable at Day 28 post last dose). 
Additionally, for all parts, an interim PK analysis of available serum 
SOL-116 concentration data will be reviewed as part of the dose 
escalation assessment. Any available blood PK data will be reviewed as 
part of the dose escalation assessment. 
Table 8-6 – 
Assignment of 
Study Codes to 
Subjects/Patients 
Cohorts MD1 and MD2 added 
Section 8.11.1 -
Pharmacokinetic 
Parameters 
In multiple dosing part, Ctrough, time to steady state and accumulation 
ratio will also be assessed. 
Attainment of steady-state conditions will be determined by visual 
inspection of the trough pre-dose serum concentrations. 
Section 10.2 – 
Analysis Sets 
Three Five different analysis sets are defined. Subjects/patients who 
withdraw from the study, or who have missing data, will be included in 
the statistical analyses provided that they are eligible for inclusion in the 
analysis population as described below. 
10.3.1 – 
Pharmacokinetic 
Statistical 
Analysis 
Attainment of steady-state conditions will be determined by visual 
inspection of the trough pre-dose serum concentrations. 
10.8 – 
Exploratory 
Analyses 
A definition of the exploratory parameters is described in Section 8.11.4. 
Exploratory parameters will be listed individually, displayed in 
appropriate graphics and summarized using descriptive statistics. The PD 
(exploratory) set will be used. Also, the PP set and the “all-treated 
set” will be used. 
10.9 – Interim 
Safety Report 
For Parts 1 and 2, the iInterim safety analysis will be conducted by the 
SRC on safety/tolerability and available PK data up to and including 14 
days post-dose after completion of at least 6 evaluable subjects per 
treatment group (subject assessed as pharmacokinetically evaluable at 
Day 14). For Part 3, the interim safety analysis will be conducted by 

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the SRC on safety/tolerability and available PK data up to and 
including 28 days post last dose after completion of at least 6 
evaluable subjects per treatment group (subject assessed as 
pharmacokinetically evaluable at Day 28 post last dose.  
10.10 – Clinical 
Study Report 
Safety and tolerability parameters as well as PK and exploratory 
parameters (BSSL, CRP, ESR and S-calprotectin) will be evaluated in 
a Clinical Study Report. Certain exploratory parameters may be 
reported separately. 
 

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Amendment 2, dated 24 February 2023, original protocol issued 15 September 2022 and 
Amendment 1 dated 30 November 2020. 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20EC of the European Parliament and the Council of the European Union. 
In this amendment, updates were made to the maximum number of study drug injections and 
maximum volume per injection. In addition, the duration of residence in the clinic and the 
number of ambulant visits for patients’ participation in Part 2 of the study has been changed 
and some additional updates have been made.  
Section 
Update 
Header 
30 November 2022 24 February 2023, Amendment 1 Amendment 2 
Title Page 
Document status/version Amendment 1 Amendment 2 
Date 30 November 2022 24 February 2023 
Synopsis - 
Treatments 
The actual dose for Cohort 2 to Cohort 5 and the dose regimen for the 
optional additional cohort of healthy subjects (Cohort 6) will be based on 
the safety and PK results of all preceding cohorts. Furthermore, based on 
the safety and PK results of all preceding cohorts the number of SC 
injections given to administer the single dose in Cohort 2 to Cohort 6 may 
be increased to 2 or 3up to 4 injections. 
In 1a cohort of up to 8 RA patients (6 active and 2 placebo will be 
randomized and dosed) (Cohort 7), one of the single doses tested in 
healthy subjects will be tested. 
There should be at least 48 hours between administration of SOL-116 and 
the proceedingpreceding methotrexate (MTX) dose and at least 48 hours 
between administration of SOL-116 and the subsequent MTX dose. 
Synopsis – 
Summary of 
Study Design 
On Day 1, all subjects/patients will receive SOL-116 in a fasted state (after 
an overnight fast of at least 10 hours). Subjects/patients will be released 
from the clinic on Day 4, (Part 1) or Day 2 (Part 2), after all required 
study procedures are completed and if medically justified. If medically 
indicated and/or based on emerging data, patients in Part 2 may be 
asked to return on Day 3 for additional safety assessments (optional 
visit). Furthermore, in both parts the clinic stay may be extended up to 
Day 7. Subjects if medically indicated and/or based on emerging data. 
In total, subjects/patients will return to the clinic for 6 (Part 1) or up to 
8 (Part 2) ambulant visits up to Day 63. Subjects/patients will return to 
the clinic on Day 90 for an EOS/follow-up visit. 
Table 5-2 Visit 
and Assessment 
Schedule – Part 
2 
Residence in the clinic was reduced to 3 days (discharge on Day 2), so 
visit numbers were updated and footnote 2 was added. 
2. 
Day 3 (Visit 3) is optional. In case of safety concerns after 
discharge on Day 2, patients may be asked to return on Day 3 for the 
assessments as presented. 

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QuantiFERON test*** 
4.0 x 1 
4.0 
Cytokine/chemokine 
panel 
2.0 x 6 
12.0 
Anti-CCP antibodies 
3.5 x 1 
3.5 
α-tocopherol 
6.0 x 3 
18.0 
S-calprotectin 
analysis 
2.0 x 6 
12.0 
Sample for future 
exploratory analysis 
5.5 x 6 
33.0 
Total blood volume* 
 
327.7 
 
 
 
 
* If the Day 3 visit does not take place, one less PK of 4.0 mL and 
one less BSSL sample of 4 mL will be collected. That would decrease 
the total blood volume to 319.7 mL. 
Section 8.4.3.1 – 
Concomitant 
Medication 
There should be at least 48 hours between administration of SOL-116 
and the proceedingpreceding MTX dose and at least 48 hours between 
administration of SOL-116 and the subsequent MTX dose. 
Section 8.5.5 – 
Study Drug 
Administration 
SOL-116 will be administered as abdominal SC injection(s). The 
injection volume will be no more than 12.0 mL per injection. The 
number of SC injections given to administer the single dose in Cohort 2 
to Cohort 7 may be increased to 2 or 3 up to 4 injections. 
In Part 2, there should be at least 48 hours between administration of 
SOL-116 and the proceedingpreceding MTX dose and at least 48 hours 
between administration of SOL-116 and the subsequent MTX dose. 

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Amendment 1, dated 30 November 2022, original protocol issued 15 September 2022. 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20EC of the European Parliament and the Council of the European Union. 
In this amendment updates were made to existing in- and exclusion criteria and two exclusion 
criteria were added, the sample volumes for PK, BSSL and future exploratory analysis samples 
were increased, the separate mention of sampling for inflammatory biomarkers (except BSSL) 
has been removed throughout the protocol as the analysis is already performed with safety lab 
samples, a clarification was made to the physical examination section, time points for α-
tocopherol status determination were updated and the sample matrix for the PK analysis was 
changed from plasma to serum. 
Section 
Update 
Header 
15 September 2022 30 November 2022, Version 2 Amendment 1 
Title Page 
Document status/version Version 2 Amendment 1  
Date 15 September 2022 30 November 2022 
Section 4 List of 
Abbreviations 
Cmax Maximum observed plasma serum concentration 
Synopsis 
– 
Center / Country 2 centers:  
QPS Netherlands B.V., Groningen, The Netherlands. 
QPS Netherlands B.V., Leeuwarden, The Netherlands. 
Synopsis 
– 
Inclusion 
Criteria 
3. 
Normal clinically physical findings, apart from RA specific 
findings for RA patients, including pulse rate, blood pressure, 
electrocardiogram (ECG), physical examination, and laboratory values 
(haematological/clinical chemistry) as judged by the Investigator. 
Healthy subjects must be negative for anti-cyclic citrullinated peptide 
(CCP) and have Rheumatoid Factor <1.5 ULN at Screening. 
8. 
Fulfilling the 2010 American College of Rheumatology 
(ACR)/European Union League Against Rheumatism (EULAR) 
classification criteria for RA. 
• 
Treatment with a stable dose of MTX for at least 12 weeks prior 
to treatment start and planned to continue with MTX during the study. 
• 
Patients naïve to biological disease modifying anti-rheumatic drug 
(bDMARD). 
• 
Patients naïve to conventional/targeted synthetic disease 
modifying anti-rheumatic drug (csDMARD/tsDMARD), except for 
MTX, or who are washed out since at least 12 weeks from such therapy 
that gave inadequate response or stopped due to other medical 
reason.before study drug dosing. 
Synopsis 
– 
Exclusion 
Criteria 
13. 
Subjects/patients who are currently enrolled in or have recently 
participated in other investigational studies another interventional 
clinical study defined as having received the last intervention within 

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90 days of Screening or 5 half-lives of the study drug (whichever is 
longer).) prior to dosing of the study drug. 
15. 
Receipt of a vaccine (except COVID-19 vaccine) within 4 weeks 
prior to dosing and/or the intention to receive a vaccine during the study. 
16. 
Recent confirmed COVID-19 infection, with less than 6 weeks 
between recovery and dosing of study drug, and/or receipt of a 
COVID-19 vaccine within 6 weeks prior to dosing of the study drug 
or having the intention to receive such a vaccine within 7 weeks post 
dosing of study drug. 
18. 
Positive urine drug screen or alcohol breath test at Screening 
andor on Day -1. 
24. 
Known Gilbert’s syndrome or Screening laboratory values 
indicating Gilbert’s syndrome. 
Synopsis 
– 
Pharmacokinetic 
Parameters 
The following will be reported as plasmaserum PK parameters for SOL-
116: 
• 
Area under the concentration-time curve from time zero to infinity 
(AUC0-inf); 
• 
Maximum observed plasmaserum concentration (Cmax); 
Synopsis 
– 
Statistical 
Methodology 
Pharmacokinetic 
PlasmaSerum concentrations and PK parameters of SOL-116 will be 
listed by dose level and summarized by time point. 
Table 5-1 – Visit 
and Assessment 
Schedule Part 1 
Row Blood sampling inflammatory biomarkers (except BSSL) was 
removed. 
Footnotes 
10. 
Fasting glucose, and lipid status and α tocopherol status 
determined at Screening, pre-dose on Day 1, Day 14 and Day 35 only. α-
tocopherol status determined pre-dose on Day 1, Day 14 and Day 35 
only. CRP and ESR determined prior to dosing and 4 hours post-dose 
on Day 1, on Day 2, on Day 4, on Day 49 and on Day 90. Subjects 
should be fasting for at least 4 hours prior to blood sampling at Screening, 
and 10 hours prior to blood sampling on Day 1, Day 14 and Day 35. 
Rheumatoid factor and anti-CCP antibodies only at Screening. 
Table 5-2 – Visit 
and Assessment 
Schedule Part 2 
Row Blood sampling inflammatory biomarkers (except BSSL) was 
removed. 
Footnotes 
10. 
Fasting glucose, and lipid status and α tocopherol status 
determined at Screening, pre-dose on Day 1, Day 14 and Day 35 only. α-
tocopherol status determined pre-dose on Day 1, Day 14 and Day 35 
only. CRP, ESR and S-calprotectin determined prior to dosing and 4 
hours post-dose on Day 1, on Day 2, on Day 4, on Day 49 and on Day 
90. Subjects should be fasting for at least 4 hours prior to blood sampling 

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at Screening, and 10 hours prior to blood sampling on Day 1, Day 14 and 
Day 35. Rheumatoid factor and anti-CCP antibodies only at Screening. 
Section 8.1.2 – 
Secondary 
Endpoints 
• 
PK of SOL-116 variables: area under the plasmaserum 
concentration-time from time zero to infinity (AUC0-inf), AUC from time 
zero to time t of the last measured concentration above the limit of 
quantification (AUC0-t), maximum observed plasmaserum concentration 
(Cmax), time to Cmax (Tmax), terminal elimination half-life (T1/2), apparent 
volume of distribution (Vz/F), apparent total body clearance (CL/F) and 
dose proportionality after single dose (based on AUC and Cmax). 
Section 8.3.3.2 – 
Procedures 
for 
Sampling 
About 3.54.0 mL blood for the PK samples will be collected via vena 
puncture or via an intravenous (IV) catheter placed in a vein in the arm 
following the local standard procedures. 
Section 8.3.3.5 - 
Bioanalysis 
The concentrations of SOL-116 in plasmaserum will be determined in the 
range 1-500 ng/mL (preliminary) using a validated ligand binding assay. 
Section 8.3.4.5 – 
Physical 
Examination 
Physical examination will be performed consisting of inspection, 
percussion, palpation, and auscultation according to the QPS Netherlands 
B.V. SOP. Clinically relevant findings that are observed after the 
screening assessment but before dosing must be recorded on the specific 
AE pagesmedical history page of the eCRF. Clinically relevant findings 
found after signing the informed consent formdosing and meeting the 
definition of an AE (new AE or worsening of previously existing 
condition) must be recorded on an AE page of the eCRF. 
Table 
8-1 
– 
Summary 
of 
Clinical 
Laboratory Tests 
Chemistry: α-tocopherolf tocopherolh 
f.  
Only at Screening, pre-dose on Day 1, on Day 14 and on Day 35. 
h. 
Only pre-dose on Day 1, Day 14 and Day 35. 
Section 8.3.6 – 
Exploratory 
Assessments 
About 3.54.0 mL blood for the BSSL samples, about 3.5 mL for the 
inflammatory biomarker, and about 2 mL for the cytokine/chemokine 
panel samples will be collected via vena puncture or via an IV catheter 
placed in a vein in the arm following the local standard procedures. 
Section 
8.3.6.1 
Exploratory 
Samples (Future 
Analysis) 
At time points specified in Table 5 1 and Table 5 2, an extra blood sample 
(5.5 mL) will be taken for future exploratory analysis of potential PK 
and/or PD markers of relevance for SOL-116. The samples will be 
discarded at the latest 10 years after the sampling occasion. 
Section 8.3.7 – 
Order 
of 
Assessments 
In case several study procedures are scheduled at the same time point, the 
following sequence should be followed pre-dose: 12-lead ECG, vital 
signs, asking for AEs, PK blood sampling, blood sampling for 
immunogenicity, blood sampling for BSSL, blood sampling for 
inflammatory biomarkers (except BSSL), blood sampling for cytokine 
and chemokine panel, blood sampling for future exploratory analysis, and 
blood sampling for clinical laboratory tests. Post-dose, the following 
sequence should be followed: PK blood sampling, blood sampling for 

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S-calprotectin 
analysis 
2.0 x 6 
12.0 
Sample for future 
exploratory analysis 
5.05 x 6 
3033.0 
Total blood volume  
 
338327.7 
**Includes S Calprotectin  
Section 8.4.1 – 
Inclusion 
Criteria 
3. 
Normal clinically physical findings, apart from RA specific 
findings for RA patients, including pulse rate, blood pressure, 
electrocardiogram (ECG), physical examination, and laboratory values 
(haematological/clinical chemistry) as judged by the Investigator. 
Healthy subjects must be negative for anti- cyclic citrullinated 
peptide (CCP) and have Rheumatoid Factor <1.5 ULN at Screening. 
8. 
Fulfilling the 2010 American College of Rheumatology 
(ACR)/European Union League Against Rheumatism (EULAR) 
classification criteria for RA. 
• 
Treatment with a stable dose of MTX for at least 12 weeks prior 
to treatment start and planned to continue with MTX during the study. 
• 
Patients naïve to biological disease modifying anti-rheumatic drug 
(bDMARD). 
• 
Patients naïve to conventional/targeted synthetic disease 
modifying anti-rheumatic drug (csDMARD/tsDMARD), except for 
MTX, or who are washed out since at least 12 weeks from such therapy 
that gave inadequate response or stopped due to other medical 
reason.before study drug dosing. 
Section 8.4.2 – 
Exclusion 
Criteria 
13. 
Subjects/patients who are currently enrolled in or have recently 
participated in other investigational studies another interventional 
clinical study defined as having received the last intervention within 
90 days of Screening or 5 half-lives of the study drug (whichever is 
longer).) prior to dosing of the study drug. 
15. 
Receipt of a vaccine (except COVID-19 vaccine) within 4 weeks 
prior to dosing and/or the intention to receive a vaccine during the study. 
16. 
Recent confirmed COVID-19 infection, with less than 6 weeks 
between recovery and dosing of study drug, and/or receipt of a 
COVID-19 vaccine within 6 weeks prior to dosing of the study drug 
or having the intention to receive such a vaccine within 7 weeks post 
dosing of study drug. 
18. 
Positive urine drug screen or alcohol breath test at Screening 
andor on Day -1. 
24. 
Known Gilbert’s syndrome or Screening laboratory values 
indicating Gilbert’s syndrome. 
Section 8.7.1 – 
Determination of 
Dose 
Additionally, an interim PK analysis of available plasmaserum SOL-116 
concentration data will be reviewed as part of the dose escalation 
assessment. Any available blood PK data will be reviewed as part of the 
dose escalation assessment. 

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Escalation/Subse
quent Dosing 
The SRC, Principal Investigator or Lipum AB may terminate dose 
escalation at any time if continuing to a higher dose level would 
jeopardize the safety of the subjects/patients. SRC reports will be 
submitted to the Independent Ethics Committee (IEC) for approval of the 
planned dose escalation and for approval to proceed to the patientnext 
cohort. 
Section 8.11.1 – 
Pharmacokinetic 
Parameters 
The plasmaserum PK parameters for SOL-116 will be derived by non-
compartmental analysis of the plasmaserum concentration-time profiles. 
The following PK parameters have been defined: 
• 
Area under the concentration-time curve from time zero to infinity 
(AUC0-inf); 
• 
Maximum observed plasmaserum concentration (Cmax); 
Attainment of steady-state conditions will be determined by visual 
inspection of the trough plasmaserum concentrations. 
Section 8.11.1.1 – 
Calculation 
of 
Pharmacokinetic 
Parameters and 
Assumption 
The measured individual plasmaserum concentrations of SOL-116 will 
be used to directly obtain Cmax and Tmax. 
AUC0-t will be calculated according to the linear up/log down trapezoidal 
method using the measured concentration-time values above the lower 
limit of quantification (LLOQ). AUC0-inf will be calculated by combining 
AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained 
by Ct/λ, where Ct is the last plasmaserum concentration measured above 
the LLOQ and λ represents the terminal elimination rate constant 
determined by log-linear regression analysis of the measured 
plasmaserum concentrations of the terminal elimination phase. The half-
life of SOL-116 will be calculated as follows: T1/2 = ln 2 / λ. 
Section 10.3.1 – 
Pharmacokinetic 
Statistical 
Analysis 
The Per-protocol analysis set will be used for all PK analyses. Individual 
subject/patient listings will be provided. Mean and individual 
plasmaserum concentration-time profiles for SOL-116 will be presented 
graphically for each group. 
Attainment of steady-state conditions will be determined by visual 
inspection of the trough plasmaserum concentrations. 
 

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3 TABLE OF CONTENTS 
1 
Signature Page for Lipum AB ........................................................................................... 5 
2 
Signature Page for Investigators ........................................................................................ 6 
Protocol Changes Log ................................................................................................................ 7 
3 
Table of Contents ............................................................................................................. 44 
4 
List of Abbreviations ....................................................................................................... 50 
5 
Protocol Synopsis ............................................................................................................ 54 
6 
Introduction and Rationale ............................................................................................... 73 
6.1 
Background ............................................................................................................... 73 
6.1.1 
Product Characteristics ...................................................................................... 73 
6.1.2 
Mechanism of Action ......................................................................................... 73 
6.1.3 
Clinical Experience with SOL-116 (current study) ........................................... 74 
6.2 
Study Rationale ......................................................................................................... 74 
6.2.1 
Rationale for Study Design ................................................................................ 74 
6.3 
Dose Selection ........................................................................................................... 75 
6.3.1 
Selection of Starting Dose in Part 1 SAD .......................................................... 75 
6.3.2 
Selection of Dose in Part 2 (RA cohort) ............................................................ 76 
6.3.3 
Maximum Exposure (SAD) ............................................................................... 76 
6.3.4 
Selection of Starting Dose and Dose Interval in Multiple Dosing Cohort(s) .... 76 
6.3.5 
Maximum Exposure (Multiple Dosing Part) ..................................................... 77 
7 
Study Objectives .............................................................................................................. 78 
7.1 
Study Objectives for Single Dosing (Parts 1 and 2).................................................. 78 
7.2 
Study Objectives for Multiple Dosing (Part 3) ......................................................... 78 
8 
Study Design .................................................................................................................... 79 
8.1 
Endpoints ................................................................................................................... 79 
8.1.1 
Primary Endpoints (all parts) ............................................................................. 79 
8.1.2 
Secondary Endpoints ......................................................................................... 79 
8.1.2.1 
Secondary Endpoints .................................................................................. 79 
8.1.2.2 
Secondary Endpoints Part 3 only................................................................ 79 
8.1.3 
Exploratory Endpoints (all parts) ....................................................................... 79 
8.2 
Overall Study Design ................................................................................................ 79 
8.3 
Study Assessments .................................................................................................... 82 
8.3.1 
Informed Consent............................................................................................... 82 
8.3.2 
Medical History and Baseline Demographics.................................................... 82 

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8.3.2.1 
Baseline Symptoms .................................................................................... 82 
8.3.2.2 
RA Medical History, DAS28-CRP, and DAS28-ESR (RA Patients Only) 82 
8.3.2.3 
Prior and Concomitant Medications ........................................................... 82 
8.3.3 
Pharmacokinetic Assessments ........................................................................... 82 
8.3.3.1 
Timing for Sampling .................................................................................. 82 
8.3.3.2 
Procedures for Sampling ............................................................................ 82 
8.3.3.3 
Labeling ...................................................................................................... 83 
8.3.3.4 
Shipping Procedures ................................................................................... 83 
8.3.3.5 
Bioanalysis.................................................................................................. 83 
8.3.4 
Safety and Tolerability Assessments ................................................................. 83 
8.3.4.1 
Adverse Events ........................................................................................... 83 
8.3.4.2 
Vital Signs .................................................................................................. 83 
8.3.4.3 
Body Weight and Height ............................................................................ 83 
8.3.4.4 
12-lead ECG ............................................................................................... 83 
8.3.4.5 
Physical Examination ................................................................................. 84 
8.3.4.6 
Patient Global Health VAS Score (Part 2 Only) ........................................ 84 
8.3.4.7 
3-lead ECG (Telemetry) ............................................................................. 84 
8.3.4.8 
QuantiFERON® Test .................................................................................. 84 
8.3.4.9 
Chest X-ray (RA Patients Only) ................................................................. 84 
8.3.4.10 
Injection Site Reactions .............................................................................. 84 
8.3.4.11 
Laboratory Assessments ............................................................................. 84 
8.3.4.12 
Drug and Cotinine Screen ........................................................................... 85 
8.3.4.13 
Alcohol Test ............................................................................................... 86 
8.3.4.14 
Pregnancy Test ........................................................................................... 86 
8.3.4.15 
Serology ...................................................................................................... 86 
8.3.4.16 
SARS-CoV-2 Test ...................................................................................... 86 
8.3.5 
Immunogenicity ................................................................................................. 86 
8.3.6 
Exploratory Assessments ................................................................................... 86 
8.3.6.1 
Exploratory Samples (Future Analysis) ..................................................... 86 
8.3.7 
Order of Assessments ........................................................................................ 86 
8.3.8 
Allowed Time Windows for PK, PD and Safety Assessments .......................... 87 
8.3.9 
Total Blood Volume .......................................................................................... 87 
8.4 
Study Population ....................................................................................................... 89 
8.4.1 
Inclusion Criteria ............................................................................................... 89 

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8.4.2 
Exclusion Criteria .............................................................................................. 90 
8.4.3 
Diet, Activities, and Other Restrictions ............................................................. 92 
8.4.3.1 
Concomitant Medication ............................................................................ 92 
8.4.3.2 
Alcohol ....................................................................................................... 92 
8.4.3.3 
Physical Activities ...................................................................................... 92 
8.4.3.4 
Dietary Aspects........................................................................................... 92 
8.4.3.5 
Smoking ...................................................................................................... 92 
8.4.3.6 
Participation in Other Clinical Studies ....................................................... 92 
8.5 
Study Drugs ............................................................................................................... 93 
8.5.1 
Investigational Drug and Matching Placebo ...................................................... 93 
8.5.2 
Study Drug Preparation...................................................................................... 93 
8.5.3 
Study Drug Packaging ....................................................................................... 93 
8.5.4 
Study Drug Labeling .......................................................................................... 93 
8.5.5 
Study Drug Administration ................................................................................ 93 
8.5.6 
Storage and Return of Study Drug ..................................................................... 94 
8.6 
Safety Review Committee ......................................................................................... 94 
8.7 
Dose Escalation Strategy ........................................................................................... 95 
8.7.1 
Determination of Dose Escalation/Subsequent Dosing ..................................... 95 
8.7.2 
Dose Escalation Stopping Criteria ..................................................................... 96 
8.7.3 
Re-initiation of Dose Escalation ........................................................................ 97 
8.8 
Study Termination or Withdrawal of Subject/Patient from Study ............................ 97 
8.8.1 
Study Termination ............................................................................................. 97 
8.8.2 
Subject/Patient Discontinuation or Withdrawal ................................................. 97 
8.8.3 
Subject’s/Patient’s Follow-up after Study Discontinuation or Withdrawal ...... 97 
8.8.4 
Subject/Patient Replacement ............................................................................. 97 
8.9 
Treatment Exposure and Compliance ....................................................................... 98 
8.10 Treatment Assignment and Blinding......................................................................... 98 
8.10.1 Assignment of Subject/Patient Numbers ........................................................... 98 
8.10.2 Treatment Assignment ....................................................................................... 98 
8.10.3 Double-blinding ................................................................................................. 99 
8.10.4 Emergency Procedure for Unblinding ............................................................... 99 
8.11 Study Parameters ....................................................................................................... 99 
8.11.1 Pharmacokinetic Parameters .............................................................................. 99 
8.11.1.1 
Calculation of Pharmacokinetic Parameters and Assumptions ................ 100 

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8.11.2 Safety and Tolerability Parameters .................................................................. 100 
8.11.3 Immunogenicity Parameters ............................................................................ 100 
8.11.4 Exploratory Parameters .................................................................................... 101 
9 
Safety Definitions and Reporting Requirements ........................................................... 102 
9.1 
Adverse Events ........................................................................................................ 102 
9.1.1 
Definitions of Adverse Events ......................................................................... 102 
9.1.2 
Intensity of Adverse Events ............................................................................. 102 
9.1.3 
Relationship to Study Drug .............................................................................. 103 
9.1.4 
Reporting of Adverse Events ........................................................................... 104 
9.1.5 
Follow-up of Adverse Events .......................................................................... 104 
9.2 
Serious Adverse Events ........................................................................................... 104 
9.2.1 
Definitions........................................................................................................ 104 
9.2.1.1 
Serious Adverse Events ............................................................................ 104 
9.2.1.2 
Pregnancy ................................................................................................. 105 
9.2.1.3 
Hospitalization – Prolongation of Existing Hospitalization ..................... 105 
9.2.1.4 
Serious Adverse Events Related to Study-mandated Procedures ............. 105 
9.2.2 
Reporting of Serious Adverse Events .............................................................. 105 
9.2.2.1 
Before Study Drug Initiation .................................................................... 105 
9.2.2.2 
During Study Drug Administration .......................................................... 105 
9.2.2.3 
After Study Drug Administration ............................................................. 105 
9.2.2.4 
Reporting Procedures ............................................................................... 106 
9.2.3 
Follow-up of Serious Adverse Events ............................................................. 106 
10 Statistical Methodology and Analyses ........................................................................... 107 
10.1 Statistical Analysis Plan .......................................................................................... 107 
10.2 Analysis Sets ........................................................................................................... 107 
10.2.1 Sample Size ...................................................................................................... 107 
10.2.2 Procedure for Accounting for Missing, Unused, and Spurious Data ............... 107 
10.3 Pharmacokinetic Parameters ................................................................................... 108 
10.3.1 Pharmacokinetic Statistical Analysis ............................................................... 108 
10.4 Safety and Tolerability Parameters ......................................................................... 108 
10.5 Immunogenicity Parameters .................................................................................... 108 
10.6 Exposure to Study Drug .......................................................................................... 109 
10.7 Baseline Parameters and Concomitant Medications ............................................... 109 
10.8 Exploratory Analyses .............................................................................................. 109 

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10.9 Interim Safety Report .............................................................................................. 109 
10.10 Clinical Study Report .............................................................................................. 110 
11 References ...................................................................................................................... 111 
12 Procedures and Good Clinical Practice.......................................................................... 112 
12.1 Procedures ............................................................................................................... 112 
12.1.1 Protocol Amendments ...................................................................................... 112 
12.1.1.1 
Non-substantial Amendment .................................................................... 112 
12.1.1.2 
Substantial Amendment ............................................................................ 112 
12.1.1.3 
Urgent Amendment .................................................................................. 112 
12.1.2 Site Monitoring ................................................................................................ 112 
12.1.3 Data Management ............................................................................................ 113 
12.1.3.1 
Data Collection ......................................................................................... 113 
12.1.3.2 
Database Management and Quality Control ............................................. 113 
12.1.4 Recording of Data and Retention of Documents ............................................. 114 
12.1.5 Audit ................................................................................................................ 114 
12.1.6 Handling of Study Drug(s)............................................................................... 114 
12.1.7 Publication of Study Results ............................................................................ 115 
12.1.8 Disclosure and Confidentiality ........................................................................ 115 
12.1.9 Stopping rules for Subject/Patient ................................................................... 115 
12.1.10 Premature Termination or Suspension of the Study ........................................ 115 
12.2 Good Clinical Practice ............................................................................................ 116 
12.2.1 Ethics and Good Clinical Practice ................................................................... 116 
12.2.2 Quality Control and Quality Assurance ........................................................... 116 
12.2.3 Independent Ethics Committee / Institutional Review Board.......................... 116 
12.2.4 Informed Consent and Recruitment ................................................................. 116 
12.2.5 Compensation to Subjects/Patients and Investigators...................................... 117 
13 Structured Risk Analysis ............................................................................................... 118 
13.1 Potential Issues of Concern ..................................................................................... 118 
13.1.1 Level of Knowledge About Mechanism of Action .......................................... 118 
13.1.2 Previous Exposure of Human Beings with the Test Product(s) and/or Products 
with a Similar Biological Mechanism ........................................................................... 118 
13.1.3 Can the Primary or Secondary Mechanism be Induced in Animals and/or in Ex-
vivo Human Cell Material? ............................................................................................ 118 
13.1.4 Selectivity of the Mechanism to Target Tissue in Animals and/or Human Beings
 
119 

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13.1.5 Analysis of Potential Effect ............................................................................. 119 
13.1.6 Pharmacokinetic Considerations ...................................................................... 119 
13.1.7 Study Population .............................................................................................. 119 
13.1.8 Interaction with Other Products ....................................................................... 119 
13.1.9 Predictability of Effect ..................................................................................... 120 
13.1.10 Can Effects be Managed? ................................................................................ 120 
13.2 Synthesis.................................................................................................................. 120 
13.3 Category study......................................................................................................... 120 
 
List of tables 
Table 5-1: Visit and Assessment Schedule – Part 1 ................................................................ 64 
Table 5-2: Visit and Assessment Schedule – Part 2 ................................................................ 67 
Table 5-3: Visit and Assessment Schedule for Repeated Dosing Part (every Q4W dosing) – 
Part 3 ........................................................................................................................................ 70 
Table 8-1: Summary of Clinical Laboratory Tests .................................................................. 85 
Table 8-2: Allowed Time Windows ........................................................................................ 87 
Table 8-3: Blood Volume (Part 1) ........................................................................................... 87 
Table 8-4: Blood Volume (Part 2) ........................................................................................... 88 
Table 8-5: Blood Volume (Part 3) ........................................................................................... 89 
Table 8-6: Assignment of Study Codes to Subjects/Patients ................................................... 98 
 

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4 LIST OF ABBREVIATIONS 
ACR 
American College of Rheumatology 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
aPTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
ATC 
Anatomic Therapeutic Chemical 
AUC 
Area under the concentration-time curve 
AUC0-inf 
AUC from time zero to infinity 
AUC0-t 
AUC from time zero to time t of the last measured concentration above the 
limit of quantification 
AUC0-tau 
AUC from time zero to the ending of the dosing interval 
bDMARD 
Biological disease modifying anti-rheumatic drug 
BMI 
Body mass index 
BSSL 
Bile salt-stimulated lipase 
CAIA 
Collagen antibody induced arthritis 
CCP 
Cyclic citrullinated peptide 
CIA 
Collagen induced arthritis 
CL/F 
Clearance 
Cmax 
Maximum observed serum concentration 
COVID-19 
Coronavirus disease 2019 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
csDMARD 
Conventional synthetic disease modifying anti-rheumatic drug 
Cmax, ss 
Maximum plasma concentration at steady state concentration 
Css 
Concentration at steady state 
Ct 
Last concentration measured above LLOQ 
CV% 
Coefficient of variation 
DA 
Dark Agouti 
DAS28 
Disease activity score 28 
DAS28-CRP 
DAS28 with CRP 

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DAS28-ESR 
DAS28 with ESR 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EOS 
End-of-study 
ESR 
Erythrocyte sedimentation rate 
EU 
European Union 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
EULAR 
European Alliance of Associations for Rheumatology 
FDA 
Food and Drug Administration 
FIH 
First-in-human 
FSH 
Follicle stimulating hormone 
FU 
Follow-up 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyltransferase 
GMP 
Good Manufacturing Practice 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HDL 
High-density lipoprotein 
HIV 
Human immunodeficiency virus 
hsCRP 
High sensitive C-reactive protein 
ICH 
International Council for Harmonization (of Technical Requirements for 
Pharmaceuticals for Human Use) 
IEC 
Independent ethics committee 
IFNγ 
Interferon gamma 
IL 
Interleukin 
INR 
International normalized ratio 
IP-10 
Interferon gamma inducible protein 10 
IRB 
Institutional review board 
ISF 
Investigator Site File 
IU 
International Unit 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IP 
Intraperitoneal  

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IV 
Intravenous(ly) 
KO 
Knockout 
LDH 
Lactate dehydrogenase 
LDL 
Low-density lipoprotein 
LH 
Luteinizing hormone 
LLOQ 
Lower limit of quantification 
MABEL 
Minimum anticipated biological effect level 
MedDRA 
Medical Dictionary for Regulatory Activities 
MD 
Multiple dosing 
MP 
Monitoring plan 
MCP 
Monocyte chemoattractant protein 
MTX 
N 
Methotrexate 
Number of subjects/patients 
NHP 
Non-human primate 
NOAEL 
No observed adverse effect level 
PCV 
Packed cell volume 
PD 
Pharmacodynamic(s) 
PIA 
Pristane induced arthritis 
PK 
Pharmacokinetic(s) 
PKAP 
Pharmacokinetic analysis plan 
PR 
PR interval of the ECG 
PT 
Prothrombin time 
Q4W 
Every fourth week 
QA 
Quality assurance 
QRS 
QRS interval of the ECG 
QTc 
Corrected QT interval 
QTcF 
Corrected QT interval using Fridericia’s formula 
RA 
Rheumatoid arthritis 
RBC 
Red blood cell 
RDW-CV 
Red blood cell distribution width 
RR 
RR interval of the ECG 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 

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SARS-CoV-2 
Severe acute respiratory syndrome-coronavirus-2 
SC 
Subcutaneous(ly) 
SD 
Standard deviation 
SOC 
System organ class 
SOP 
Standard operating procedure 
SRC 
Safety review committee 
SU 
Safety unit 
SUSAR 
Suspected unexpected serious adverse reaction 
T1/2 
Terminal elimination half-life 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 
THC 
Tetrahydrocannabinol 
Tmax 
Time to reach Cmax 
TNFα 
Tumor necrosis factor alpha 
tsDMARD 
Targeted synthetic disease modifying anti-rheumatic drug 
ULN 
Upper limit of normal 
US 
United States 
VAS 
Visual analogue scale 
Vz/F 
Apparent volume of distribution 
WBC 
White blood cell 
WHO 
World Health Organization 
WT 
Wild type 

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5 PROTOCOL SYNOPSIS 
TITLE 
A Randomized, Double-Blind, Placebo-Controlled, First-
in-Human Phase I Study Evaluating Safety, Tolerability 
and Pharmacokinetics of Single Ascending Doses of  
SOL-116 (a Humanized Monoclonal Anti-BSSL Antibody) 
in Healthy Subjects and Patients with Rheumatoid Arthritis 
PHASE 
I 
CENTERS / COUNTRY  
QPS Netherlands B.V., Groningen, The Netherlands 
CHDR, Leiden, The Netherlands 
ICON, Groningen, The Netherlands 
INVESTIGATIONAL 
DRUG AND DOSAGE 
FORM 
SOL-116 for subcutaneous (SC) administration 
ROUTE OF 
ADMINISTRATION 
SC injection 
OBJECTIVES 
Objectives for single dosing (Parts 1 and 2) 
 
Primary objective: 
• To evaluate the safety and tolerability of single 
ascending doses of SOL-116 in healthy subjects and 
rheumatoid arthritis (RA) patients. 
Secondary objective: 
• To determine single dose pharmacokinetic (PK) 
characteristics of SOL-116 in healthy subjects and RA 
patients. 
• To assess the immunogenicity of SOL-116 after single 
SC doses in healthy subjects and RA patients.  
Exploratory objectives: 
• To evaluate the effect of single ascending doses of  
SOL-116 on bile salt-stimulated lipase (BSSL) 
concentration in the blood of healthy subjects and RA 
patients. 
• To evaluate the pharmacodynamic (PD) effect of single 
ascending doses of SOL-116 on inflammatory 
biomarkers in the blood of healthy subjects and RA 
patients. 
Objectives for multiple dosing (Part 3) 
Primary objective: 
• To evaluate the safety and tolerability of multiple dosing 
of SOL-116 in healthy subjects. 

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Secondary objective: 
• To determine multiple dose PK characteristics of SOL-
116 in healthy subjects. 
• To assess the immunogenicity of SOL-116 after multiple 
SC doses in healthy subjects. 
Exploratory objectives: 
• To evaluate the effect of multiple doses of SOL-116 on 
BSSL concentration in the blood of healthy subjects.  
• To evaluate the PD effect of multiple doses of SOL-116 
on inflammatory biomarkers in the blood of healthy 
subjects. 
DESIGN 
This is a randomized, double-blind, placebo-controlled 
Phase I, first-in-human (FIH) study. 
TREATMENTS 
Part 1 
Up to 5 single doses are planned to be tested in 5 cohorts of 
8 healthy subjects (6 active, 2 placebo) (Cohort 1 to Cohort 
5). One additional cohort (Cohort 6) of 8 healthy subjects 
(6 active, 2 placebo) may be added based on emerging data, 
i.e. in total 40 or 48 subjects will be randomized and dosed.  
The starting dose in Cohort 1 will be 0.075 mg/kg SOL-116 
given as a single SC injection. The actual dose for Cohort 2 
to Cohort 5 and the dose regimen for the optional additional 
cohort of healthy subjects (Cohort 6) will be based on the 
safety and PK results of all preceding cohorts. Furthermore, 
based on the safety and PK results of all preceding cohorts 
the number of SC injections given to administer the single 
dose in Cohort 2 to Cohort 6 may be increased to up to 4 
injections. The maximum dose increment will be 3. The 
highest dose to be tested in man will not exceed a dose 
predicted to generate exposures above those at NOAEL in 
the monkey (plasma concentrations of 1240 μg/mL (Cmax) 
or an AUC0-168h of 164000 μg/mL*h). 
Sentinel dosing will be employed in all cohorts. Thus, 
within each cohort initially 1 subject will receive SOL-116 
and 1 subject will receive placebo. The remaining 6 subjects 
of the cohort may be dosed at least 48 hours after dosing of 
the initial 2 subjects of the cohort, provided no clinically 
significant safety issues, as judged by the Investigator, are 
noted in the 48 hours after dosing of the initial 2 subjects of 
the cohort. 
After each cohort completes dosing, a dose escalation 
Safety Review Committee (SRC) meeting will take place. 
Escalation to the next higher dose level may occur only after 
evaluation of the safety/tolerability and available PK data 

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up to and including 14 days post-dose of at least 6 evaluable 
subjects (subject assessed as pharmacokinetically evaluable 
at Day 14) and after approval by the independent ethics 
committee (IEC). This time point may be adjusted based on 
the PK data of previous cohorts if the SRC recommends. 
Part 2 
In a cohort of up to 8 RA patients (6 active and 2 placebo 
will be randomized and dosed) (Cohort 7), one of the single 
doses tested in healthy subjects will be tested. 
The cohort with RA patients (Cohort 7) will be run after the 
completion of all cohorts with healthy subjects. The dose 
level of Cohort 7 will be determined based on the safety and 
PK results of all preceding cohorts and will not exceed that 
of the already given dose levels in healthy subjects. There 
should be at least 24 hours between administration of 
SOL-116 and the preceding methotrexate (MTX) dose and 
at least 24 hours between administration of SOL-116 and 
the subsequent MTX dose. 
Sentinel dosing will be employed. Thus, initially 1 patient 
will receive SOL-116 and 1 patient will receive placebo. 
The remaining 6 subjects of the cohort can be dosed at least 
48 hours after dosing, provided no clinically significant 
safety issues, as judged by the Investigator, are noted in the 
48 hours after dosing of the initial 2 patients of the cohort. 
Part 3 
Up to two multiple dosing cohorts of 8 healthy subjects (6 
active, 2 placebo) (Cohorts MD1 and MD2) are planned, i.e. 
in total up to 16 subjects will be randomized and dosed.  
The starting dose in Cohort MD1 will be 3.0 mg/kg SOL-
116 given as SC injection(s). 
 
 
 
The dosing period will not exceed 12 weeks, but dosing 
frequency may be altered (higher or lower) compared to the 
first multiple dosing cohort.  
Sentinel dosing will be employed in all cohorts. Thus, 
within each cohort initially 1 subject will receive SOL-116 
and 1 subject will receive placebo. The remaining 6 subjects 
of the cohort may be dosed at least 48 hours after dosing of 
the initial 2 subjects of the cohort, provided no clinically 
significant safety issues, as judged by the Investigator, are 
noted in the 48 hours after dosing of the initial 2 subjects of 
the cohort. 
After each cohort completes dosing, a dose escalation SRC 
meeting will take place. Escalation to the next MD dose 

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cohort may occur only 
after evaluation of the 
safety/tolerability and available PK data up to and including 
28 days post last dose of at least 6 evaluable subjects 
(subject assessed as pharmacokinetically evaluable at Day 
28) and after approval by the IEC. This time point may be 
adjusted based on the PK data of previous cohorts if the 
SRC recommends. 
SUMMARY OF STUDY 
DESIGN 
The study will be monitored by a SRC. The intent of the 
SRC is to ensure that treatment does not pose undue risk to 
subjects/patients. Safety, tolerability and available PK data 
will be assessed by the SRC after each cohort before 
ascending to the next dose level. 
Eligibility will be assessed during a screening period of up 
to 42 days. For the treatment period, subjects/patients will 
check into the clinic one day prior to dosing (Day -1). On 
Day 1, all subjects/patients will receive SOL-116 in a fasted 
state (after an overnight fast of at least 10 hours). 
Subjects/patients will be released from the clinic on Day 4 
(Part 1) or Day 2 (Part 2), after all required study procedures 
are completed and if medically justified. If medically 
indicated and/or based on emerging data, patients in Part 2 
may be asked to return on Day 3 for additional safety 
assessments (optional visit). Furthermore, in both parts the 
clinic stay may be extended up to Day 7 if medically 
indicated and/or based on emerging data. In total, 
subjects/patients will return to the clinic for 6 (Part 1) or up 
to 8 (Part 2) ambulant visits up to Day 63. Subjects/patients 
will return to the clinic on Day 90 for an EOS/follow-up 
visit. 
A multiple dosing part will be performed in healthy subjects 
where, in the first multiple dosing cohort, each subject will 
receive a total of four doses every fourth week (Q4W): at 
baseline (D1) and Days 29, 57 and 85. With a dose interval 
of 28 days, it is estimated that with the half-life of SOL-116 
(assessed in the SAD) concentrations at, or close to, steady 
state will be reached after the fourth dose. The subjects are 
followed up until Day 169. 
Based on SRC recommendation, the visit schedule may be 
adjusted. 
STUDY POPULATION 
Up to 48 healthy male or female subjects and 8 male or 
female RA patients (for Parts 1 and 2, respectively). 
Preferably at least 3 out of 8 subjects per cohort should be 
of the least represented sex (female or male), respectively. 
The study also includes up to 16 healthy adult subjects in 
one or two multiple dosing cohorts (Part 3). 

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INCLUSION CRITERIA 
The following criteria must be met by all subjects/patients 
considered for study participation: 
1. Willing and able to give written informed consent for 
participation in the study and is willing and able to 
abide by the study restrictions. 
2. Males and females aged between 18 and 65 years 
(inclusive) at Screening. For patients in the RA cohort, 
an age interval between 18 and 70 years (inclusive). 
3. Normal clinically physical findings, apart from RA 
specific findings (including deviating laboratory values 
e.g., mild anaemia or swollen joints) for RA patients, 
including pulse rate, blood pressure, electrocardiogram 
(ECG), physical examination, and laboratory values 
(haematological/clinical chemistry) as judged by the 
Investigator. Healthy subjects must be negative for 
anti-cyclic citrullinated peptide (CCP) and have 
Rheumatoid Factor <1.5 ULN at Screening. 
4. For Parts 1 and 3, body mass index (BMI) between 19.0 
and 30.0 kg/m2 and body weight between 50 to 100 kg 
(inclusive) at Screening. For Part 2, body weight 
between 50 to 120 kg (inclusive) at Screening. 
5. Sexually active male patients participating in the study 
must use a barrier method of contraception (condom) 
and refrain from sperm donation during the study and 
for 150 days after last dosing if their female sexual 
partner is of childbearing potential. Acceptable methods 
of birth control for female partners of male subjects are: 
hormonal contraceptives (oral contraceptives, implant 
or injection), intrauterine device (placed at least 1 
month before the start of the study). Surgical 
sterilization of male patients can be accepted as a form 
of birth control if the sterilization procedure took place 
at least 6 months prior to the start of the study. 
6. Females of childbearing potential must during the 
study and for at least 230 days after dosing utilise a 
method of contraception that can achieve a failure rate 
of less than 1% per year when used consistently and 
correctly. Such highly effective birth control methods 
include: 
• combined (estrogen and progestogen containing) 
hormonal contraception associated with inhibition 
of ovulation: 
i. oral 
ii. intravaginal 
iii. transdermal 
• progestogen-only 
hormonal 
contraception 
associated with inhibition of ovulation: 
i. oral 
ii. injectable 

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iii. implantable 
• intrauterine device (IUD) 
• intrauterine hormone-releasing system (IUS) 
• bilateral tubal occlusion 
• vasectomized partner 
• sexual abstinence 
7. Females of non-childbearing potential must fulfil one 
of the following: 
• Irreversibly surgically sterile i.e., hysterectomy, 
bilateral salpingectomy, the fallopian tubes have 
been blocked or sealed (sterilisation), and bilateral 
oophorectomy. 
• Spontaneous amenorrhoea during the last 12 months 
prior to enrolment, and having follicle stimulating 
hormone (FSH) levels in the postmenopausal range 
(i.e. ≥ 30 mIU/mL) at Screening. 
The following inclusion criterion is only applicable for RA 
patients: 
8. Fulfilling the 2010 American College of Rheumatology 
(ACR)/European Union League Against Rheumatism 
(EULAR) classification criteria for RA. 
• Treatment with MTX for at least 12 weeks prior to 
treatment start and planned to continue with MTX 
during the study; if the MTX dose was changed 
during the 12-week period, such a patient may be 
included in the study based on Investigator 
judgement. 
• Patients naïve to biological disease modifying anti-
rheumatic drug (bDMARD) or who are washed out 
(at least 5 half-lives) from such therapy before 
study drug dosing. 
• Patients naïve to conventional/targeted synthetic 
disease 
modifying 
anti-rheumatic 
drug 
(csDMARD/tsDMARD), except for MTX, or who 
are washed out since at least 12 weeks from such 
therapy before study drug dosing. 
• Use of oral glucocorticosteroids is allowed if 
equivalent to ≤5 mg/day of prednisolone on a 
stable dose for a least 4 weeks prior to dosing 
(Day 1) and expected to remain on that dose level 
for at least 4 weeks after dosing (Day 1). 
EXCLUSION CRITERIA 
Subjects/Patients will be excluded if they meet any of the 
following criteria: 
1. History of any clinically significant acute inflammatory 
joint disease (for the RA cohort; other than RA). 
2. Any chronic or long-lasting disease which may 
interfere with the study objectives or jeopardise the 

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safety of the subjects/patients as judged by the 
Investigator or responsible physician (for the RA 
cohort; other than RA). 
3. Ongoing infection on Day-1. 
4. Serious infection treated with antibiotics and evaluated 
by physician in the past 14 days prior to Day -1. 
5. Current treatment with heparin products. 
6. Use of any prescription or non-prescription drugs 
(excluding paracetamol, hormonal contraceptives), 
antacids, herbal, and dietary supplements (including St 
John’s Wort) within 14 days (or 28 days if the drug is a 
potential hepatic enzyme inducer) or 5 half-lives 
(whichever is longer) prior to the first dose of study 
drug for healthy subjects and within 4 weeks prior to 
the first dose of study drug for RA patients, unless in 
the opinion of the Investigator the medication will not 
interfere with the study procedures or compromise 
subject/patient safety. In RA patients, MTX and folic 
acid use are exempted. 
7. Aspartate 
aminotransferase 
(AST) 
and 
alanine 
aminotransferase (ALT) ≥ 2.0 times upper limit of 
normal (ULN); alkaline phosphatase and bilirubin ≥ 1.5 
times the ULN at Screening or on Day -1. At Screening, 
these assessments may be repeated once, at the 
discretion of the Investigator. 
8. Serum creatinine > 1.5 times the ULN or estimated 
glomerular filtration rat (eGFR) <60 at Screening or on 
Day -1 (for Part 1 and Part 3). Estimated glomerular 
filtration rat (eGFR) <60 at Screening or on Day -1 (for 
Part 2). At Screening, these assessments may be 
repeated once, at the discretion of the Investigator. 
9. Subjects/patients who have experienced surgery within 
6 months of the screening visit that could negatively 
impact on the subject’s/patient’s participation in the 
opinion of a Principal Investigator or responsible 
physician. 
10. High blood pressure at Screening or on Day -1, judged 
as clinically relevant by a Principal Investigator or 
responsible physician. A repeat test may be performed. 
11. Positive test for human immunodeficiency virus (HIV), 
hepatitis B surface antigen (HBsAg), or hepatitis C 
virus antibody (anti-HCV) at Screening. 
12. Having evidence of active tuberculosis (TB) or latent 
TB at Screening as assessed by chest X-ray (RA 
patients 
only) 
and/or 
by 
QuantiFERON®-test. 
Applicable for RA patients only: in case of rescreening 
within three months after Screening, negative results 
from the initial chest X-ray and/or QuantiFERON®-test 
performed during Screening do not need to be repeated. 

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13. Subjects/patients who are currently enrolled in or have 
recently participated in another interventional clinical 
study defined as having received the last intervention 
within 90 days or 5 half-lives of the study drug 
(whichever is longer) prior to dosing (Parts 1 and 2) vs. 
prior to first dosing (Part 3) of the study drug. 
14. History or known hypersensitivity or allergy, or any 
form of allergic reactions to any excipients in the study 
drug or to humanized or murine monoclonal antibodies 
(or immunoglobulins). 
15. Receipt of a vaccine within 4 weeks (COVID-19 
vaccine within 6 weeks) prior to dosing and/or the 
intention to receive a vaccine during the study. 
Deviation from this should be judged by the 
Investigator and in dialogue with the Sponsor. 
16. Recent confirmed COVID-19 infection, with less than 
6 weeks between recovery and dosing of study drug. 
17. Blood or plasma donation within 3 months of 
enrolment. 
18. Positive urine drug screen or alcohol test at Screening 
or on Day -1. 
19. History of drug or alcohol abuse, at the discretion of the 
Investigator, within past 12 months prior to Screening. 
20. The subject currently smokes or uses nicotine-
containing products. Former smokers will be eligible, 
provided they have not smoked for at least 1 month 
prior to Screening. Positive cotinine test results at 
Screening or on Day -1 are reason for exclusion. Such 
positive test results can be repeated once to exclude 
environmental influence on the subject. 
21. A positive pregnancy test or lactation at Screening or 
on Day -1. 
The following exclusion criteria are only applicable for RA 
patients: 
22. Intra-articular or systemic corticosteroid injection 
within 4 weeks prior to dosing. 
23. Current or expected need of other immunosuppressant 
medication 
except 
MTX 
and/or 
intra-articular 
corticosteroid injections. 
24. Known Gilbert’s syndrome or Screening laboratory 
values indicating Gilbert’s syndrome. 
SAFETY / TOLERABILITY 
PARAMETERS 
The following are defined as safety/tolerability parameters: 
• Clinical laboratory evaluations; 
• Injection site reactions; 
• Adverse events (AEs); 
• Immune reactions (e.g. hypersensitivity, cytokine 
release syndrome, immunogenicity); 
• Vital signs; 

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• Physical examination; 
• ECGs (3-lead telemetry and 12-lead ECGs); 
• Concomitant medications/therapy. 
PHARMACOKINETIC 
PARAMETERS 
The following will be reported as serum PK parameters for 
SOL-116: 
• Area under the concentration-time curve from time 
zero to infinity (AUC0-inf); 
• Maximum observed serum concentration (Cmax); 
• Time to Cmax (Tmax); 
• AUC from time zero to time t of the last measured 
concentration above the limit of quantification  
(AUC0-t); 
• Terminal elimination half-life (T1/2); 
• Apparent volume of distribution (Vz/F); 
• Apparent total body clearance (CL/F). 
 
In multiple dosing part, also:  
• Minimum observed serum concentration at steady 
state (Ctrough), time to steady state, accumulation 
ratio. 
IMMUNOGENICITY 
PARAMETERS 
The following are defined as immunogenicity parameters: 
• Development of anti-drug antibodies (ADA). If a 
subject is confirmed ADA-positive, the following 
may be determined: 
o Estimation of ADA titers 
o Neutralizing capacity 
o Isotype 
o Epitope map 
EXPLORATORY 
PARAMETERS 
The following are defined as exploratory parameters: 
• BSSL concentration; 
• Inflammatory biomarkers (except BSSL): C-
reactive protein (CRP), erythrocyte sedimentation 
rate 
(ESR) 
for 
all 
subjects/patients, 
and  
S-calprotectin and high sensitive CRP (hsCRP) 
(only RA patients); 
• Cytokine/chemokine panel (including but not 
limited to IFNγ, IL-1β, IL-6, IL-10, IL-12, IL-18, 
MCP-1 and TNFα); 
• Flow cytometry panel (only RA patients); 
• Whole blood stimulation assays (only RA patients). 
STATISTICAL 
METHODOLOGY  
Safety and tolerability 
AEs will be coded with MedDRA and a summary frequency 
table of AEs will be provided. The severity and relationship 
of AEs to study drug will also be summarized. Furthermore, 

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if any serious adverse events (SAEs) occur, a summary of 
SAEs will be described and listed in a table. 
ECG variables (3-lead (telemetry) and 12-lead ECG), vital 
sign measurements and laboratory measurements will be 
summarized at each time point using mean, median, 
standard deviation, min, max, number of available 
observations, and change from baseline. Individual subject 
listings of ECG data, vital signs data, physical examination 
data, 
immune 
reactions, 
injection 
site 
reactions, 
concomitant 
medication/therapy 
and 
laboratory 
measurements will be provided. 
Pharmacokinetic 
Serum concentrations and PK parameters of SOL-116 will 
be listed by dose level and summarized by time point. The 
following descriptive statistics will be calculated: number 
of subjects (N), arithmetic mean, standard deviation, 
geometric mean, median, minimum, maximum, and 
coefficient of variation (CV%). Nominal blood sampling 
times will be used in the summary. 
Dose proportionality will be assessed for SOL-116. 
Immunogenicity and exploratory 
Immunogenicity and exploratory parameters will be listed 
individually, displayed in appropriate graphics and 
summarized using descriptive statistics. 
 

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16. Up until study drug administration. 
17. Spare subjects not immediately included in the study may be kept in the clinic until it is decided whether these subjects are to be included. If subjects are included > 48 hours after admission in 
the clinic on Day -1, the Day -1 assessments have to be repeated. 

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2. 
Day 3 (Visit 3) is optional. In case of safety concerns after discharge on Day 2, patients may be asked to return on Day 3 for the assessments as presented. 
3. 
If the clinic visit is extended up to and including Day 7, Visit 5 will not take place. In that case, all blood sampling scheduled for Day 8 will be performed on Day 6 or Day 7, at the discretion 
of the Investigator. 
4. 
Not to be performed when this assessment was done within 3 weeks prior to dosing and result is available. In case of rescreening within three months after Screening, negative results from the 
initial QuantiFERON® test performed during Screening do not need to be repeated. 
5. 
If a chest X-ray was performed within the past three weeks prior to dosing and documentation is available, it is not necessary to repeat the chest X-ray. In case of rescreening within three months 
after Screening, negative results from the initial chest X-ray performed during Screening do not need to be repeated. 
6. 
On Day 1: Prior to dosing and 1 and 4 hours post-dose. 
7. 
The 28-joint assessment will only be performed on Day -1 (baseline). 
8. 
There should be at least 24 hours between administration of SOL-116 and the preceding MTX dose and at least 24 hours between administration of SOL-116 and the subsequent MTX dose. 
9. 
Four (4) hours after the (last) injection on Day 1, on Day 2, Day 4, Day 8 and thereafter as needed. 
10. Triplicate at Screening and on Day- 1. On Day 1: 1 and 4 hours post-dose. 
11. From 1 hour pre-dose until 6 hours post-dose. 
12. Serum at Screening, urine at all other timepoints. 
13. On Day 1 prior to dosing, and at 1, 4, 8, 24 (Day 2), 48 (Day 3, optional) and 72 hours (Day 4) post-dose. 
14. On Day 1 prior to dosing. Based on emerging data, collection time points may be updated. 
15. Only collected and analysed when the patient has given consent for the collection and future analysis of this sample in the informed consent form. 
16. Fasting glucose and lipid status determined at Screening, pre-dose on Day 1, Day 14 and Day 35. α-tocopherol status determined pre-dose on Day 1, Day 14 and Day 35 only. S-calprotectin and 
hsCRP determined prior to dosing and 4 hours post-dose on Day 1, on Day 2, on Day 4, on Day 21, on Day 49 and on Day 90. Subjects should be fasting for at least 4 hours prior to blood 
sampling at Screening, and 10 hours prior to blood sampling on Day 1, Day 14 and Day 35. Rheumatoid factor and anti-CCP antibodies only at Screening. Urinalysis only at Screening, on 
Day -1, on Day 2, on Day 8, on Day 14, on Day 21, and on Day 90. At Screening, laboratory assessments may be repeated once, at the discretion of the Investigator. 
17. If medically indicated and/or based on emerging data, the clinic stay may be extended up to Day 7. 
18. Starting from study drug administration. 
19. Prior to dosing and 4 hours post-dose. 
20. 4 hours post-dose. 
21. Up until study drug administration. 
22. Spare patients not immediately included in the study may be kept in the clinic until it is decided whether these patients are to be included. If subjects are included > 48 hours after admission in 
the clinic on Day -1, the Day -1 assessments have to be repeated. 
 
 
 

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12. If medically indicated and/or based on emerging data, the clinic stay may be extended up to Day 7. 
13. Starting from first study drug administration. 
14. On Day 1: Prior to dosing and 1 and 4 hours post-dose. After the other doses: Prior to dosing and 4 hours post-dose. 
15. Day 92 only 
16. Assessed for four (4) hours after each injection and thereafter as needed. 
17. Prior to dosing and 4 hours post-dose. 
18. Pre-dose, 4 and 24 hours post-dose 
19. Pre-dose only. 
20. Pre-dose and 4 hours post dose. 
21. Day 113 only. 
22. Day 88 only 
23. Days 92 and 113 only. 
24. Up until first study drug administration. 
 
 

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6 INTRODUCTION AND RATIONALE 
6.1 Background 
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disease characterized 
by varying numbers of swollen, stiff and painful joints typically in hands and feet, but any joint 
may be affected. With time, erosion of joints and bone results in varying degree of disability 
and loss of quality of life. RA may also have systemic manifestations affecting other organs, 
e.g., skin, heart, lungs and/or eyes causing severe complications. The etiology of the disease is 
not fully understood but the expert opinion is that a combination of genetic predisposition and 
environmental factors as trigger is needed. Examples of triggers are cigarette smoking, 
infections, and trauma. The global prevalence of RA is 0.3% to 1% with significant variation 
between populations and the disease is threefold more common among women than men [1]. 
It affects all age groups but the most common age at onset is 40-60 years [2]. RA is a 
heterogeneous disease with substantial variation between individuals both with respect to 
number of joints and organs affected and the activity of the disease, something that is also 
reflected on the cellular and molecular level. This in turn is likely part of the explanation why 
a substantial proportion of the RA patients do not respond satisfactorily to current treatment 
alternatives, and why there is still a great medical need for new treatment alternatives [3]. 
6.1.1 Product Characteristics 
The intended product SOL-116 is a humanized monoclonal anti-Bile Salt-Stimulated Lipase 
(BSSL) antibody of the IgG4 S228P subclass 
   
The therapeutic approach for the antibody SOL-116 is to block the function of BSSL in chronic 
inflammatory conditions with a lead indication to prevent inflammation and joint destruction 
in patients diagnosed with RA. 
6.1.2 Mechanism of Action 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
For more details on the pre-clinical studies conducted with SOL-116, please see the 
Investigator’s Brochure [6]. 

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6.1.3 Clinical Experience with SOL-116 (current study) 
To date, Part 1 has been concluded. Five cohorts with 8 healthy subjects (male and female) 
per cohort have been administered SOL-116 or placebo (6 active and 2 placebo), up to 
6.075 mg/kg single dose. There were 25 males and 15 females enrolled, age range 22 to 64 
years. No subjects dropped out, few adverse events and no serious adverse event (SAE) were 
reported. There were no clinically relevant changes from baseline reported on the following: 
vital signs, ECG parameters, telemetry, clinical laboratory, physical examination. The serum 
SOL-116 exposure (AUC, Cmax) increased in an approximately dose-proportional manner.  
In Part 2, the enrolment of rheumatoid arthritis (RA)-patients is currently ongoing. Part 3, 
with multiple dosing is ongoing. 
6.2 Study Rationale 
SOL-116 is a new monoclonal antibody targeting BSSL that is developed for the treatment of 
RA. There are preliminary data showing increased concentration of serum BSSL in patients 
with inflammatory conditions compared to healthy individuals [7]. 
The aim of the study is to achieve safety, tolerability and PK data to support continued 
development of the candidate drug. 
This clinical study will be conducted in compliance with the protocol, Good Clinical Practice 
(GCP) and the applicable regulatory requirement(s). 
6.2.1 Rationale for Study Design 
The design of the SAD study is based on the aim to study safety, tolerability and 
pharmacokinetics (PK) of selected doses of SOL-116 in a limited number of healthy subjects 
and in a cohort of RA patients. 
Fertile women are allowed to enter the study. SOL-116 has not been investigated with regards 
to reproductive toxicology, hence sexually active male subjects must use a barrier method of 
contraception and female subjects of childbearing potential must utilize a method that can 
achieve a failure rate of less than 1% per year when used consistently and correctly are 
considered as highly effective birth control methods. 
The adaptive study design allows for flexible dose escalation and involves careful monitoring 
of the subject’s well-being. The study will provide important PK data to support the design of 
further studies. The time points for PK blood sampling were selected based on data obtained 
from previous studies with other monoclonal antibodies.  
A placebo control will be used to establish the frequency and magnitude of changes in 
endpoints that may occur in the absence of active treatment. Randomization will be used to 
minimize bias in the assignment of subjects to dose groups and to increase the likelihood that 
known and unknown subject attributes (e.g., demographic and baseline characteristics) are 
evenly balanced across treatment groups. Blinded treatment will be used to reduce potential 
bias during data collection and evaluation of endpoints.   
One cohort with RA patients will be enrolled to obtain safety and PK data and to observe any 
difference in PK parameters between healthy subjects and RA patients. This information is 
important for future clinical studies. 
In the multiple dosing part in healthy subjects, up to two multiple dosing cohorts (6:2) will be 
conducted sequentially, but with an overlap, where the 28-day (i.e., Tmax plus one half-life) 
safety and PK data post last dose will be assessed by a Safety Review Committee (SRC). The 

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SRC will decide if, and at what dose level, the subsequent cohort may commence. For the first 
multiple dosing cohort (MD1), the dose and dose interval will be based on all available SAD 
data and PK modelling data. The subjects will be followed for approximately 90 days post-
treatment in order to get an estimate of clearance and elimination half-life after multiple dosing. 
6.3 Dose Selection 
6.3.1 Selection of Starting Dose in Part 1 SAD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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6.3.2 Selection of Dose in Part 2 (RA cohort) 
In Part 1 of the study, doses up to 6.075 mg/kg SOL-116 resulted in an exposure of 12 800 
(µg/mL*h) in healthy subjects, with no safety or tolerability issues. 
To allow for a direct comparison of plasma SOL-116 PK in healthy subjects versus RA 
patients, a previously used dose was selected for the RA patient cohort. The planned SC dose 
for the RA SAD-cohort is 2.025 mg/kg SOL-116, i.e., 3-fold lower than the highest dose 
tested in healthy subjects but believed to result in an exposure within the predicted 
therapeutic concentration range in humans.  
 
 
 
 
 
 
 
 
 
 
 
6.3.3 Maximum Exposure (SAD) 
 
  
6.3.4 Selection of Starting Dose and Dose Interval in Multiple Dosing Cohort(s) 
The starting dose in the first multiple dosing cohort (MD1) will be 3.0 mg/kg. This dose level 
is predicted to result in an exposure within the same order of magnitude as the expected 
therapeutic concentration in humans. 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
The subjects will be administered study drug approximately every four weeks for 12 weeks 
(total of 4 doses). This administration schedule was selected for the first multiple dosing 

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cohort from the projected time to reach steady state, which is based on the half-life of SOL-
116 observed in Part 1 of this study (approximately 19 days).  
 
 
 
 
 
 
 
  
6.3.5 Maximum Exposure (Multiple Dosing Part) 
 
 
 
 
 

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7 STUDY OBJECTIVES 
7.1 Study Objectives for Single Dosing (Parts 1 and 2) 
Primary objective: 
• To evaluate the safety and tolerability of single ascending doses of SOL-116 in healthy 
subjects and RA patients. 
Secondary objective: 
• To determine single dose PK characteristics of SOL-116 in healthy subjects and RA 
patients. 
• To assess the immunogenicity of SOL-116 after single SC doses in healthy subjects and 
RA patients. 
Exploratory objectives: 
• To evaluate the effect of single ascending doses of SOL-116 on BSSL concentration in 
the blood of healthy subjects and RA patients.  
• To evaluate the PD effect of single ascending doses of SOL-116 on inflammatory 
biomarkers in the blood of healthy subjects and RA patients. 
7.2 Study Objectives for Multiple Dosing (Part 3) 
Primary objective: 
• To evaluate the safety and tolerability of multiple dosing of SOL-116 in healthy 
subjects. 
Secondary objective: 
• To determine multiple dose PK characteristics of SOL-116 in healthy subjects. 
• To assess the immunogenicity of SOL-116 after multiple SC doses in healthy subjects. 
Exploratory objectives: 
• To evaluate the effect of multiple doses of SOL-116 on BSSL concentration in the 
blood of healthy subjects.  
• To evaluate the PD effect of multiple doses of SOL-116 on inflammatory biomarkers 
in the blood of healthy subjects. 
 

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8 STUDY DESIGN 
8.1 Endpoints 
8.1.1 Primary Endpoints (all parts) 
• Adverse events (type, frequency, severity, and relationship of adverse events (AEs) to 
study 
drug 
treatment), 
clinical 
laboratory 
evaluations 
(including 
blood 
haematology/plasma biochemistry analyses and urinalyses), immune reactions, vital 
signs, electrocardiogram (ECG) and injection site reactions. 
8.1.2 Secondary Endpoints 
8.1.2.1 Secondary Endpoints  
• PK of SOL-116 variables for single dose regimens: area under the serum 
concentration-time from time zero to infinity (AUC0-inf), AUC from time zero to time 
t of the last measured concentration above the limit of quantification (AUC0-t), area 
under the serum concentration-time from time zero to the end of dosing interval 
(AUC0-tau) (Part 3), maximum observed serum concentration (Cmax), time to Cmax 
(Tmax), terminal elimination half-life (T1/2) (Parts 1 and 2), apparent volume of 
distribution (Vz/F) (Parts 1 and 2), apparent total body clearance (CL/F) (Parts 1 and 
2) and dose proportionality after single dose (based on AUC and Cmax) (Part 1). 
• Incidence and titre of anti-drug antibodies (ADA) to SOL-116. 
8.1.2.2 Secondary Endpoints Part 3 only 
PK of SOL-116 variables for the last dose: area under the serum concentration-time from 
time zero to the end of dosing interval (AUC0-tau), maximum observed serum concentration 
(Cmax), time to Cmax (Tmax), minimum observed serum concentration (Ctrough), average serum 
concentration (Cave), apparent total body clearance at steady state (CLss/F), time to steady 
state, accumulation ratio in Cmax and AUC0-tau. 
8.1.3 Exploratory Endpoints (all parts) 
• Change from baseline in BSSL concentration in blood. 
• Change from baseline in inflammatory biomarkers, i.e. serum C-reactive protein (CRP), 
erythrocyte sedimentation rate (ESR) for all subjects/patients and S-calprotectin and 
high sensitive CRP (hsCRP) (only RA patients). 
• Change from baseline in plasma concentration of cytokine/chemokine panel (including 
but not limited to IFNγ, IL-1β, IL-6, IL-10, IL-12, IL-18, MCP-1 and TNFα). 
• Change form baseline in other exploratory markers (RA patients only), based on flow 
cytometry panel and whole blood stimulation assay. 
8.2 Overall Study Design 
This is a randomized, double-blind, placebo-controlled phase I, first-in-human (FIH) study 
designed to evaluate the safety, tolerability and PK of single SC ascending doses of SOL-116 
in healthy subjects and adult RA patients (Parts 1 and 2) and multiple SC doses in healthy 
subjects (Part 3).  
The study will be monitored by a Safety Review Committee (SRC). The intent of the SRC is 
to ensure that treatment does not pose undue risk to subjects/patients. Safety, tolerability and 

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available PK data will be assessed by the SRC after each cohort before ascending to the next 
dose level. Based on SRC recommendation, the visit schedule may be adjusted. 
Part 1 
Eligibility will be assessed during a screening period of up to 28 days. For the treatment period, 
subjects will check into the clinic one day prior to dosing (Day -1). On Day 1, all subjects will 
receive SOL-116 in a fasted state (after an overnight fast of at least 10 hours). Subjects will be 
released from the clinic on Day 4, after all required study procedures are completed and if 
medically justified. If medically indicated and/or based on emerging data, the clinic stay may 
be extended up to Day 7. Subjects will return to the clinic for 6 ambulant visits up to Day 63. 
Subjects will return to the clinic on Day 90 for an EOS/follow-up visit. 
Up to 5 single doses are planned to be tested in 5 cohorts of 8 healthy subjects (6 active, 2 
placebo) (Cohort 1 to Cohort 5). One additional1 cohort (Cohort 6) of 8 healthy subjects (6 
active, 2 placebo) may be added based on emerging data, i.e. in total 40 or 48 subjects will be 
randomized and dosed.  
The starting dose in Cohort 1 will be 0.075 mg/kg SOL-116 given as a single SC injection. The 
actual dose for Cohort 2 to Cohort 5 and the dose regimen for the optional additional cohort of 
healthy subjects (Cohort 6) will be based on the safety and PK results of all preceding cohorts. 
Furthermore, based on the safety and PK results of all preceding cohorts the number of SC 
injections given to administer the single dose in Cohort 2 to Cohort 6 may be increased to up 
to 4 injections. The maximum dose increment will be 3. The highest dose to be tested in man 
will not exceed a dose predicted to generate exposures above those at NOAEL in the monkey 
(plasma concentrations of 1240 μg/mL (Cmax) or an AUC0-168h of 164000 μg/mL*h). 
Sentinel dosing will be employed in all cohorts. Thus, within each cohort initially 1 subject 
will receive SOL-116 and 1 subject will receive placebo. The remaining 6 subjects of the cohort 
may be dosed at least 48 hours after dosing of the initial 2 subjects of the cohort, provided no 
clinically significant safety issues, as judged by the Investigator, are noted in the 48 hours after 
dosing of the initial 2 subjects of the cohort. 
After each cohort completes dosing, a dose escalation SRC meeting will take place. Escalation 
to the next higher dose level may occur only after evaluation of the safety/tolerability and 
available PK data up to and including 14 days post-dose of at least 6 evaluable subjects (subject 
assessed as pharmacokinetically evaluable at Day 14) and after approval by the IEC. This time 
point may be adjusted based on the PK data of previous cohorts if the SRC recommends. 
Please refer to Table 5-1 for an overview of ambulatory visits and residence in the clinic. 
Part 2 
Eligibility will be assessed during a screening period of up to 42 days. For the treatment period, 
patients will check into the clinic one day prior to dosing (Day -1). On Day 1, all patients will 
receive SOL-116 in a fasted state (after an overnight fast of at least 10 hours). Patients will be 
released from the clinic on Day 2, after all required study procedures are completed and if 
medically justified. If medically indicated and/or based on emerging data, patients may be 
asked to return on Day 3 for additional safety assessments (optional visit). Furthermore, the 
clinic stay may be extended up to Day 7, if medically indicated and/or based on emerging data. 
 
1 The optional 6th cohort in healthy subjects was not run 

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In total, patients will return to the clinic for up to 8 ambulant visits up to Day 63. Patients will 
return to the clinic on Day 90 for an EOS/follow-up visit. 
In a cohort of up to 8 RA patients (6 active, 2 placebo will be randomized and dosed) (Cohort 
7), one of the single doses tested in healthy subjects was selected, i.e., 2.025 mg/kg will be 
tested (see Section 6.1.3 and Section 6.3.2). 
The cohort with RA patients (Cohort 7) will be run after the completion of all cohorts with 
healthy subjects. The dose level of Cohort 7 will be determined based on the safety and PK 
results of all preceding cohorts and will not exceed that of the already given dose levels in 
healthy subjects. There should be at least 24 hours between administration of SOL-116 and the 
preceding methotrexate (MTX) dose and at least 24 hours between administration of SOL-116 
and the subsequent MTX dose. 
Sentinel dosing will be employed. Thus, initially 1 patient will receive SOL-116 and 1 patient 
will receive placebo. The remaining 6 subjects of the cohort can be dosed at least 48 hours after 
dosing, provided no clinically significant safety issues, as judged by the Investigator, are noted 
in the 48 hours after dosing of the initial 2 patients of the cohort. 
Please refer to Table 5-2 for an overview of ambulatory visits and residence in the clinic. 
Part 3 
The multiple dosing part will be in healthy subjects where, in the first multiple dosing cohort, 
each subject will receive a total of four doses every fourth week (Q4W): at baseline (D1) and 
Days 29, 57 and 85. With a dose interval of 28 days, it is estimated that with the half-life of 
SOL-116 (assessed in the SAD) concentrations at, or close to, steady state will be reached after 
the fourth dose. 
Eligibility will be assessed during a screening period of up to 28 days. For the first dose, 
subjects will check into the clinic one day prior to dosing (Day -1). On Day 1, all subjects will 
receive SOL-116 or placebo. Subjects will be released from the clinic on Day 2, after all 
required study procedures are completed and if medically justified. If medically indicated 
and/or based on emerging data, the clinic stay may be extended up to Day 7. Subjects will 
return to the clinic for 15 ambulant visits up to Day 154. Subjects will return to the clinic on 
Day 169 for an EOS/follow-up visit. After the second and third dose, a phone contact will be 
made (3 to 7 days after the dose) with the subject to ensure no new adverse events or if new 
medication has been added. 
Up to two multiple dosing cohorts of 8 healthy subjects (6 active, 2 placebo) (Cohorts MD1 
and MD2) are planned, i.e. in total up to 16 subjects will be randomized and dosed.  
The starting dose in Cohort MD1 will be 3.0 mg/kg SOL-116 given as SC injection(s) (see 
Section 0). The actual dose and dose interval for the potential Cohort MD2 will be based on 
the safety and PK results of all preceding SAD and MD cohort (see Section 6.3.5). The dosing 
period will not exceed 12 weeks, but dosing frequency may be altered (higher or lower) 
compared to the first multiple dosing cohort.  
Sentinel dosing will be employed in all cohorts. Thus, within each cohort initially 1 subject 
will receive SOL-116 and 1 subject will receive placebo. The remaining 6 subjects of the cohort 
may be dosed at least 48 hours after dosing of the initial 2 subjects of the cohort, provided no 
clinically significant safety issues, as judged by the Investigator, are noted in the 48 hours after 
dosing of the initial 2 subjects of the cohort. 

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After each cohort completes dosing, a dose escalation SRC meeting will take place (see 
Section 8.7.1). Escalation to the next MD dose cohort may occur only after evaluation of the 
safety/tolerability and available PK data up to and including 28 days post last dose of at least 
6 evaluable subjects (subject assessed as pharmacokinetically evaluable at Day 28) and after 
approval by the IEC. This time point may be adjusted based on the PK data of previous cohorts 
if the SRC recommends. 
Please refer to Table 5-3 for an overview of ambulatory visits and residence in the clinic. 
8.3 Study Assessments 
8.3.1 Informed Consent 
After adequate explanation of the aims, methods, objectives of the study and potential hazards 
of the study drug and after the subject/patient has had ample time to consider their participation, 
a written informed consent from each individual participating in this study will be obtained. 
8.3.2 Medical History and Baseline Demographics 
All relevant medical history will be documented. 
Baseline demographics including sex, age, race and ethnicity will be recorded. 
8.3.2.1 Baseline Symptoms 
A baseline symptom is defined as an event that occurs between subject’s signing of the 
informed consent form until the first administration of the study drug. Such events are not AEs 
and will be recorded as baseline symptoms in the Medical History Log in the eCRF. 
8.3.2.2 RA Medical History, DAS28-CRP, and DAS28-ESR (RA Patients Only) 
The following information will be noted at Screening: Year of diagnosis, joints affected at 
diagnosis and present, rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies 
positivity (positive or negative), disease activity at diagnosis and at screening (mild, moderate, 
severe), other organs affected by RA, surgery needed (joints or other), previous RA treatment 
(since diagnosis). 
The disease activity score 28 (DAS28) for RA with CRP (DAS28-CRP) and the DAS-28 for 
ESR (DAS28-ESR) will be determined on Day -1 (baseline). 
8.3.2.3 Prior and Concomitant Medications 
All relevant medications taken from 2 weeks prior to Screening (4 weeks for RA cohort) until 
end-of-study (EOS) or started during the study will be recorded on the Concomitant 
Medications page. For RA cohort, see also Section 8.3.2.2. 
Concomitant Medications initiated, stopped, up-titrated or down-titrated for an AE will be 
recorded on the Concomitant Medications page. This includes concomitant medication for RA 
(if applicable). 
8.3.3 Pharmacokinetic Assessments 
8.3.3.1 Timing for Sampling 
Table 5-1, Table 5-2 and Table 5-3 provide an overview of all PK blood sampling time points. 
8.3.3.2 Procedures for Sampling 
About 4.0 mL blood for the PK samples will be collected via vena puncture or via an 
intravenous (IV) catheter placed in a vein in the arm following the local standard procedures. 

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Information on equipment and further details on the procedures on the sampling are 
documented in a separate instruction manual. 
8.3.3.3 Labeling 
PK tubes will be pre-labeled. 
8.3.3.4 Shipping Procedures 
The site staff will take care of the shipment of the samples. Samples must be sent to QPS 
Netherlands B.V. laboratory at time intervals agreed with the Sponsor. The samples must be 
packed securely together with completed shipment forms in polystyrene-insulated shipping 
containers together with enough dry ice to last for 48 hours.  
8.3.3.5 Bioanalysis 
The concentrations of SOL-116 in serum will be determined in the range 1-500 ng/mL 
(preliminary) using a validated ligand binding assay. Concentrations will be calculated by 
interpolation from a calibration curve. Quality control samples will be analyzed throughout the 
study. Their measured concentrations will be used to determine overall precision and accuracy 
of the analyses. 
8.3.4 Safety and Tolerability Assessments 
The definitions, reporting, and follow-up of AEs and serious adverse events (SAEs) are 
described in Section 9. Table 5-1, Table 5-2 and Table 5-3 provide an overview of all time 
points on which safety assessments will be performed. 
8.3.4.1 Adverse Events 
Adverse events will be recorded according to the local standard operating procedure 
(SOP)/Work instruction of the clinic. 
8.3.4.2 Vital Signs 
Vital sign assessments will be performed according to the local SOP of the clinic and will 
include measurements of supine blood pressure, pulse rate, and body temperature. Vital sign 
measurements will be collected after the subject/patient has been resting for 5 minutes in a 
supine position. 
8.3.4.3 Body Weight and Height 
The subject’s/patient’s body weight will be measured using a validated balance according to 
the local SOP of the clinic. Body weight will be recorded with 1 decimal. The 
subject’s/patient’s height is measured without wearing shoes. The body mass index (BMI) will 
be calculated from the weight and height recorded at Screening. BMI (kg/m2) = weight 
(kg)/height2 (m2). 
8.3.4.4 12-lead ECG 
Subjects/patients will be in a supine position for 5 minutes prior to the measurements. ECGs 
will be evaluated and classified as normal/abnormal according to the local SOP of the clinic. 
In case of “abnormal”, the abnormality has to be described. The Investigator will judge if the 
abnormal ECG findings are considered clinically significant. Clinically significant abnormal 
findings (as judged by the Investigator) will be recorded as AE. 
HR, PR, QRS, and QT will be provided on the print-out of the ECG apparatus or in the 
electronic Muse system (RA patients only). Bazett (QT/RR1/2)/Fridericia (QT/RR1/3) QTc is 
automatically calculated by the ECG apparatus and provided on the print-out or in Muse (RA 

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patients only). For the screening ECG and the Day -1 ECG, three recordings will be made with 
an interval of approximately 1 minute between recordings. Evaluation of average recordings 
will be performed according to the local SOP of the clinic. Any repeat measurement will also 
be done in triplicate. All other recordings will be single (one recording of at least 3 complexes). 
8.3.4.5 Physical Examination 
Physical examination will be performed consisting of inspection, percussion, palpation, and 
auscultation according to the local SOP of the clinic. For Part 2, this will also (at baseline) 
include a 28-joint status (number of swollen joints and number of tender joints). Clinically 
relevant findings that are observed after the screening assessment but before dosing must be 
recorded on the specific medical history page of the eCRF. Clinically relevant findings found 
after dosing and meeting the definition of an AE (new AE or worsening of previously existing 
condition) must be recorded on an AE page of the eCRF. 
8.3.4.6 Patient Global Health VAS Score (Part 2 Only) 
In Part 2, the patients will be asked (at baseline) to fill in a Patient Global Health VAS score. 
8.3.4.7 3-lead ECG (Telemetry) 
Telemetry monitoring will be set on alarm and used for evaluation of any cardiac event. It will 
be performed according to the local SOP of the clinic. Results will be analyzed by the 
Investigator and significant findings will be reported. Clinically significant abnormal findings 
(as judged by the Investigator) will be recorded as AE. 
8.3.4.8 QuantiFERON® Test 
The QuantiFERON® test will be performed at Screening to test for active tuberculosis (TB) or 
latent TB unless this assessment was done within 3 weeks prior to dosing and results are 
available. Applicable for RA patients only: in case of rescreening within three months after 
Screening, negative results from the initial QuantiFERON®-test performed during Screening 
do not need to be repeated. For this test 4 tubes of 1 mL blood each will be taken. 
8.3.4.9 Chest X-ray (RA Patients Only) 
Only for RA patients, a chest X-ray will be taken at Screening to test for active TB or latent 
TB. If a chest X-ray was performed within the past three weeks prior to dosing and 
documentation is available, it is not necessary to repeat the chest X-ray. In case of rescreening 
within three months after Screening, negative results from the initial chest X-ray performed 
during Screening do not need to be repeated. 
8.3.4.10 Injection Site Reactions 
Injection site reactions (dryness, redness, swelling, pain/tenderness and itching) will be 
assessed by the Investigator at specific time points (see Table 5-1, Table 5-2 and Table 5-3). 
Clinically significant abnormal findings (as judged by the Investigator) will be recorded as AE. 
8.3.4.11 Laboratory Assessments 
Clinically significant laboratory abnormalities must be reported by the Investigator as AE or 
SAE as appropriate (see Section 9). At Screening, laboratory assessments may be repeated 
once, at the discretion of the Investigator. 
For Part 1 and 2, the blood samples will be taken under fasted conditions at time points 
specified in Table 5-1 and Table 5-2 (due to fasting glucose and/or lipid and α-tocopherol 
status). On these days, subjects/patients will not be allowed to eat or drink (except water) for a 
period of 4 hours (Screening) or 10 hours (other time points as specified in Table 5-1 and Table 

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8.3.4.13 Alcohol Test 
An alcohol test (breath test or urine) will be performed according to the local SOP of the clinic. 
8.3.4.14 Pregnancy Test 
A serum pregnancy test will be performed at Screening. A urine pregnancy test will be performed 
on Day -1, Visit 7 (Parts 1 and 3), Visit 8 (Part 3) and Visit 9 (Parts 2 and 3) and at the EOS 
examination (or at early termination) (all parts). The results must be available prior to dosing. 
8.3.4.15 Serology 
At Screening, virus serology will be assessed (HIV, hepatitis B and hepatitis C). 
8.3.4.16 SARS-CoV-2 Test 
COVID-19 testing will be performed at the time point described in Table 5-1. A check on 
health status will be performed and body temperature will be measured before the 
subject/patient enters the clinic on Day -1 (Part 1). For Parts 2 and 3, COVID-19 testing is not 
mandatory as recommendations have changed since the study started. Testing for COVID-19 
will be done at the discretion of the investigator, based on clinical symptoms. 
8.3.5 Immunogenicity 
Blood samples will be taken to check for the presence of ADA at time points specified in  
Table 5-1, Table 5-2 and Table 5-3. 
About 3.5 mL blood for the ADA samples will be collected via vena puncture or via an IV 
catheter placed in a vein in the arm following the local standard procedures. 
8.3.6 Exploratory Assessments 
Blood samples will be taken to check BSSL concentration, cytokine/chemokine panel 
(including but not limited to IFNγ, IL-1β, IL-6, IL-10, IL-12, IL-18, MCP-1, and TNFα), flow 
cytometry panel (only RA patients), and whole blood stimulation (only RA patients) at the time 
points specified in Table 5-1, Table 5-2 and Table 5-3. 
About 2 mL or 4 mL (2 mL for Part 3 and 4 mL for Parts 1 and 2) blood for the BSSL samples, 
and about 2 mL for the cytokine/chemokine panel samples will be collected via vena puncture 
or via an IV catheter placed in a vein in the arm following the local standard procedures. In 
Part 2, about 10 mL for the flow cytometry panel and about 10 mL for the whole blood 
stimulation assay will be collected. 
8.3.6.1 Exploratory Samples (Future Analysis) 
At time points specified in Table 5-1, Table 5-2 and Table 5-3, extra blood samples (5.5 mL in 
total) will be taken for future exploratory analysis of potential PK and/or PD markers of 
relevance for SOL-116. The samples will be discarded at the latest 10 years after the sampling 
occasion. 
8.3.7 Order of Assessments 
In case several study procedures are scheduled at the same time point, the following sequence 
should be followed pre-dose: 12-lead ECG, vital signs, asking for AEs, PK blood sampling, 
blood sampling for immunogenicity, blood sampling for BSSL, blood sampling for cytokine 
and chemokine panel, blood sampling for flow cytometry panel (Part 2 only), blood sampling 
for whole blood stimulation assay (Part 2 only), blood sampling for future exploratory analysis, 
and blood sampling for clinical laboratory tests. Post-dose, the following sequence should be 
followed: PK blood sampling, blood sampling for immunogenicity, blood sampling for BSSL, 
blood sampling for cytokine and chemokine panel, blood sampling for flow cytometry panel 

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accepted as a form of birth control if the sterilization procedure took place at least 6 months 
prior to the start of the study. 
6. Females of childbearing potential must during the study and for at least 230 days after last 
dosing utilise a method of contraception that can achieve a failure rate of less than 1% per 
year when used consistently and correctly. Such highly effective birth control methods 
include: 
• combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
• progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
• intrauterine device (IUD) 
• intrauterine hormone-releasing system (IUS) 
• bilateral tubal occlusion 
• vasectomized partner 
• sexual abstinence 
7. Females of non-childbearing potential must fulfil one of the following: 
• Irreversibly surgically sterile i.e., hysterectomy, bilateral salpingectomy, the fallopian 
tubes have been blocked or sealed (sterilization), and bilateral oophorectomy. 
• Spontaneous amenorrhoea during the last 12 months prior to enrolment, and having 
follicle stimulating hormone (FSH) levels in the postmenopausal range (i.e. ≥ 30 
mIU/mL) at Screening. 
The following inclusion criterion is only applicable for RA patients: 
8. Fulfilling the 2010 American College of Rheumatology (ACR)/European Union League 
Against Rheumatism (EULAR) classification criteria for RA [8]. 
• Treatment with MTX for at least 12 weeks prior to treatment start and planned to 
continue with MTX during the study; if the MTX dose was changed during the 12-week 
period, such a patient may be included in the study based on Investigator judgement. 
• Patients naïve to biological disease modifying anti-rheumatic drug (bDMARD) or who 
are washed out (at least 5 half-lives) from such therapy before study drug dosing. 
• Patients naïve to conventional/targeted synthetic disease modifying anti-rheumatic drug 
(csDMARD/tsDMARD), except for MTX, or who are washed out since at least 12 
weeks from such therapy before study drug dosing. 
• Use of oral glucocorticosteroids is allowed if equivalent to ≤5 mg/day of prednisolone 
on a stable dose for a least 4 weeks prior to dosing (Day 1) and expected to remain on 
that dose level for at least 4 weeks after dosing (Day 1). 
8.4.2 Exclusion Criteria 
Subjects/Patients will be excluded if they meet any of the following criteria: 
1. History of any clinically significant acute inflammatory joint disease (for the RA cohort; 
other than RA). 
2. Any chronic or long-lasting disease which may interfere with the study objectives or 
jeopardise the safety of the subjects/patients as judged by the Investigator or responsible 
physician (for the RA cohort; other than RA). 

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3. Ongoing infection on Day-1. 
4. Serious infection treated with antibiotics and evaluated by physician in the past 14 days 
prior to Day -1. 
5. Current treatment with heparin products. 
6. Use of any prescription or non-prescription drugs (excluding paracetamol, hormonal 
contraceptives), antacids, herbal, and dietary supplements (including St John’s Wort) 
within 14 days (or 28 days if the drug is a potential hepatic enzyme inducer) or 5 half-lives 
(whichever is longer) prior to the first dose of study drug for healthy subjects and within 4 
weeks prior to the first dose of study drug for RA patients, unless in the opinion of the 
Investigator the medication will not interfere with the study procedures or compromise 
subject/patient safety. In RA patients, MTX and folic acid use are exempted. 
7. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.0 times upper 
limit of normal (ULN); alkaline phosphatase and bilirubin ≥ 1.5 times the ULN at Screening 
or on Day -1. At Screening, these assessments may be repeated once, at the discretion of 
the Investigator. 
8. Serum creatinine > 1.5 times the ULN or estimated glomerular filtration rat (eGFR) <60 at 
Screening or on Day -1 (for Part 1 and Part 3). Estimated glomerular filtration rat (eGFR) 
<60 at Screening or on Day -1 (for Part 2). At Screening, these assessments may be repeated 
once, at the discretion of the Investigator. 
9. Subjects/patients who have experienced surgery within 6 months of the screening visit that 
could negatively impact on the subject’s/patient’s participation in the opinion of a Principal 
Investigator or responsible physician. 
10. High blood pressure at Screening or on Day -1, judged as clinically relevant by a Principal 
Investigator or responsible physician. A repeat test may be performed. 
11. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen 
(HBsAg), or hepatitis C virus antibody (anti-HCV) at Screening. 
12. Having evidence of active TB or latent TB at Screening as assessed by chest X-ray (RA 
patients only) and/or by QuantiFERON®-test. Applicable for RA patients only: in case of 
rescreening within three months after Screening, negative results from the initial chest X-
ray and/or QuantiFERON®-test performed during Screening do not need to be repeated. 
13. Subjects/patients who are currently enrolled in or have recently participated in another 
interventional clinical study defined as having received the last intervention within 90 days 
or 5 half-lives of the study drug (whichever is longer) prior to dosing (Parts 1 and 2) vs. 
prior to first dosing (Part 3) of the study drug. 
14. History or known hypersensitivity or allergy, or any form of allergic reactions to any 
excipients in the study drug or to humanized or murine monoclonal antibodies (or 
immunoglobulins). 
15. Receipt of a vaccine within 4 weeks (COVID-19 vaccine within 6 weeks) prior to dosing 
and/or the intention to receive a vaccine during the study. Deviation from this should be 
judged by the Investigator and in dialogue with the Sponsor. 
16. Recent confirmed COVID-19 infection, with less than 6 weeks between recovery and 
dosing of study drug.  
17. Blood or plasma donation within 3 months of enrolment. 
18. Positive urine drug screen or alcohol test at Screening or on Day -1. 
19. History of drug or alcohol abuse, at the discretion of the Investigator, within past 12 months 
prior to Screening. 
20. The subject currently smokes or uses nicotine-containing products. Former smokers will 
be eligible, provided they have not smoked for at least 1 month prior to Screening. Positive 

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cotinine test results at Screening or on Day -1 are reason for exclusion. Such positive test 
results can be repeated once to exclude environmental influence on the subject. 
21. A positive pregnancy test or lactation at Screening or on Day -1. 
The following exclusion criteria are only applicable for RA patients: 
22. Intra-articular or systemic corticosteroid injection within 4 weeks prior to dosing. 
23. Current or expected need of other immunosuppressant medication except MTX and/or 
intra-articular corticosteroid injections. 
24. Known Gilbert’s syndrome or Screening laboratory values indicating Gilbert’s syndrome. 
8.4.3 Diet, Activities, and Other Restrictions 
8.4.3.1 Concomitant Medication 
From 2 weeks (or 28 days if the drug is a potential hepatic enzyme inducer) or 5 half-lives 
(whichever is longer) prior to Screening (or 4 weeks for RA cohort) until the EOS, prescribed 
or over-the-counter medication (including herbal remedies) is only allowed as described in 
exclusion criterion 6. Any new concomitant medication for treatment of AEs should preferably 
be discussed beforehand with the Investigator. The occasional use of paracetamol is allowed. 
Female subjects/patients are allowed to use oral contraception, a hormonal implant or hormonal 
intra-uterine devices as contraception. RA patients only (Part 2): If there is a medical need, 
local intra-articular corticosteroid injections are permitted at the discretion of a Principal 
Investigator.  
If concomitant medication is needed during the study, this medication must be recorded on the 
eCRF, stating its generic name, time of administration, dose, route, frequency and duration, as 
well as the reason for administration. 
The patients in the RA cohort will be treated with MTX. There should be at least 24 hours 
between administration of SOL-116 and the preceding MTX dose and at least 24 hours between 
administration of SOL-116 and the subsequent MTX dose. The patients in the RA cohort are 
allowed to use folic acid.  
Part 3 only: Medications for incidental use (e.g., hay fever) may, at the Investigator’s 
discretion, be allowed during the study. 
8.4.3.2 Alcohol 
Drinking of alcoholic beverages is not permitted from 48 hours prior to each clinic visit  or 
while in the clinic.  
8.4.3.3 Physical Activities 
From 24 hours prior to each clinic visit, the subjects/patients should refrain from excessive 
physical exercise and strenuous sports activities (endurance sports). 
8.4.3.4 Dietary Aspects 
Consumption of food containing poppy seeds is not allowed from 24 hours prior to Screening 
and prior to Day -1. 
8.4.3.5 Smoking 
Smoking is not permitted from one month prior to Screening up to and including the EOS visit. 
8.4.3.6 Participation in Other Clinical Studies 
Study subjects are not allowed to participate in any other interventional clinical drug study 
during the study period. 

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8.5 Study Drugs 
Study drugs include the investigational drug SOL-116 and matching placebo administered 
during the study. 
8.5.1 Investigational Drug and Matching Placebo 
Lipum AB will provide SOL-116 and matching placebo. SOL-116 is available for clinical 
study use in the form of a solution for SC injection. Placebo is available as matching solution 
for SC administration. 
8.5.2 Study Drug Preparation 
All study drugs will be prepared (packaged and labeled in individual doses) at QPS Netherlands 
B.V. (for Part 1 and Part 3) or the pharmacy of the Leiden University Medical Center (LUMC) 
(for Part 2) by an unblinded pharmacist, or his/her designee. In order to minimize the risks of 
unblinding, the pharmacist/designee is not involved in any other aspect of the study. 
8.5.3 Study Drug Packaging 
Lipum AB will be responsible for the supply of the following drugs: 
- 
Solution containing 100 mg/mL of SOL-116. 
- 
Matching placebo. 
The study drug will be packed and dispatched in containers. A batch release certificate will be 
provided, stating that the batches have been manufactured according to good manufacturing 
practice (GMP). Study drugs are provided as a solution and supplied to the study center as a 
bulk shipment. Under the supervision of the pharmacist, the study drug will be packed per 
subject/patient for each dosing occasion, according to the randomization list. 
8.5.4 Study Drug Labeling 
The labeling complies with the applicable (local) laws and regulations. At the minimum, the 
following information will be stated on the labels: 
• Study number (LPM-116-001) 
• SOL-116 (strength) or placebo 
• Name, address of Sponsor  
• Name of the Investigator and CRO 
• Batch number 
• Subject/patient identification/treatment number 
• Quantity of dosage units 
• Route of administration (SC) and pharmaceutical dosage form 
• Directions for use 
• Storage conditions 
• Expiry date 
• “For clinical study use only” or similar wording 
8.5.5 Study Drug Administration 
SOL-116 will be administered as abdominal SC injection(s). The injection volume will be no 
more than 2.0 mL per injection. The number of SC injections given to administer the single 
dose in Cohort 2 to Cohort 7 may be increased to up to 4 injections. 
Subjects/patients will not be allowed to eat or drink (except water) from 10 hours prior to the 
administration of study drug or placebo. 

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All study drugs will be dispensed by the Investigator or a person supervised by the Investigator. 
The time of administration of SOL-116 or placebo will be recorded in the eCRF. 
In Part 3, the same applies but 4 dose administrations (with maximum 4 injections per occasion) 
will be administered with 28 days’ interval (in MD1). 
In Part 2, there should be at least 24 hours between administration of SOL-116 and the 
preceding MTX dose and at least 24 hours between administration of SOL-116 and the 
subsequent MTX dose. 
8.5.6 Storage and Return of Study Drug 
Upon receipt of the study drugs, the responsible pharmacist or her designee will inspect all 
study drugs for completeness. Subsequently, he/she must immediately return the enclosed 
acknowledgement of receipt form; duly completed and signed (the date of receipt must be 
noted). 
The pharmacist is responsible for storage of the study drug at the study site in an appropriate 
lockable room at 2–8 oC. The drug will be stored according to the instructions provided by the 
Sponsor. Only the pharmacist or his/her designee, who are otherwise not involved in the study, 
will handle the study drug. 
A Drug Preparation Protocol as well as a Drug Accountability Record must be kept current and 
should at least contain the following information: 
• Subject/patient number for whom the drug was prepared 
• Initials and date of the person who prepared the study drug 
• Date(s) on which drug was prepared and quantity of the drug prepared 
The inventory must be available for verification by the clinical research associate 
(CRA)/monitor. 
After Sponsor confirmation, all unused investigational material (drugs and packaging) must be 
returned to the Sponsor or destroyed by the site on termination of the study and after a drug 
accountability check by the CRA/monitor, listing the following: 
• All SOL-116 administered 
• All unused SOL-116 
• All SOL-116 returned at the end of the study, and the date of return/destroyed by the 
site 
The pharmacist will be responsible for the inventory and accountability of all Clinical Trial 
Material, exercising accepted pharmaceutical practices. An accurate, timely record of the 
Clinical Trial Material will be maintained. Only after completion of the study (to avoid 
breaking the blind), the Clinical Trial Material and the inventory will be available for inspection 
by the designated representatives of Lipum AB upon request. The original Drug Preparation 
Protocol and Drug Accountability Record are considered as source data and will be archived 
at the site. 
8.6 Safety Review Committee 
The study will be monitored by an SRC. The SRC is intended to ensure that the study drug 
does not pose undue risk to subjects/patients. Safety, tolerability and available PK data up to 
14 days post-dose of at least 6 evaluable subjects (subject assessed as pharmacokinetically 
evaluable at Day 14) will be assessed by the SRC prior to ascending from one dose-level cohort 
to the next-higher dose-level cohort. For Cohort 2 onwards, cumulative PK data will also be 
considered. Key PK parameters for dose escalation are Cmax (μg/mL) and AUC (μg/mL*h). A 

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dose increment of 3 will never be exceeded in selecting the next dose level. Prior to Cohort 3 
and thereafter, the SRC will also consider dose linearity. 
For Part 3, the same applies but data up to 28 days post last dose will be collected and assessed 
at the SRC. 
The SRC will be composed of the following core individuals: 
• Principal Investigator(s) or delegate(s) (delegation only when a Principal Investigator 
is not available); 
• Lipum AB chief medical officer or delegate (must be a physician); 
• QPS pharmacokineticist; 
• Other internal or external experts may be invited to participate in the review or may be 
consulted. 
8.7 Dose Escalation Strategy 
8.7.1 Determination of Dose Escalation/Subsequent Dosing 
For Part 1: The decision to escalate to the next dose level will not take place until the SRC has 
reviewed the blinded safety and tolerability data, including but not limited to vital signs, ECG 
results, clinical laboratory tests, and AEs, up to and including 14 days post-dose of at least 6 
evaluable subjects (subject assessed as pharmacokinetically evaluable at Day 14). For Part 2: 
The same applies as for Part 1 but will include 21 days data for safety/PK review. 
For Part 3: The decision to escalate to the next dose level will not take place until the SRC has 
reviewed the blinded safety and tolerability data, including but not limited to vital signs, ECG 
results, clinical laboratory tests, and AEs, up to and including 28 days (i.e., Tmax plus one half-
life) post last dose of at least 6 evaluable subjects (subject assessed as pharmacokinetically 
evaluable at Day 28 post last dose). 
Additionally, for all parts, an interim PK analysis of available serum SOL-116 concentration 
data will be reviewed as part of the dose escalation assessment. Any available blood PK data 
will be reviewed as part of the dose escalation assessment. 
After the review of each dose level, the SRC will make one of the following determinations: 
• To continue with the study as planned. The SRC agrees that adequate safety and 
tolerability have been demonstrated in accordance with the dose-escalation and 
stopping criteria). 
• To continue with the study as planned and evaluate additional or alternate time points 
for safety evaluations. Additional time points for existing safety procedures requiring 
blood collection may be added, provided that the additional time points do not result in 
the additional collection of more than 15 mL of blood. For the addition of safety 
procedures that would require blood collection more than 15 mL, an EC-approved 
protocol amendment and Informed Consent Form is required. 
• To continue with the study by:  
o Repeating a dose level. 
o Selecting an alternative dose level between the current dose level and the next 
planned dose level. 
o Selecting an alternative dose level between the current dose level and any previous 
lower dose level. 
The SRC, Principal Investigator(s) or Lipum AB may terminate dose escalation at any time if 
continuing to a higher dose level would jeopardize the safety of the subjects/patients. SRC 

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reports will be submitted to the Independent Ethics Committee (IEC) for approval of the 
planned dose escalation and for approval to proceed to the next cohort. After completion of all 
healthy subject cohorts, the report to the IEC on proceeding to the patient cohort will also 
include a cumulative interim report and a revised structured risk analysis, as applicable.    
8.7.2 Dose Escalation Stopping Criteria 
• One (1) or more subjects who receive SOL-116 experience a SAE which is considered 
to be related to the study medication. 
• Two (2) or more subjects who receive SOL-116 have QTc prolongation, defined as an 
average absolute (regardless of baseline value) QTcF >500 msec or an increase of QTcF 
>60 msec above baseline, confirmed by repeated ECG after at least 5 minutes, and 
determined post-dose. 
• Two (2) or more subjects who receive SOL-116 exhibit hypotension, defined as resting 
supine diastolic blood pressure <40 mmHg, an asymptomatic or symptomatic fall in 
systolic blood pressure to below 80 mmHg, persisting for at least 10 minutes on 
repeated assessment. 
• Two (2) or more subjects who receive SOL-116 exhibit hypertension, defined as an 
increase in resting systolic blood pressure to above 180 mmHg, persisting for at least 
10 minutes, or an increase in resting diastolic blood pressure to above 105 mmHg, 
persisting for at least 10 minutes. 
• Two (2) or more subjects who receive SOL-116 exhibit tachycardia, defined as resting 
supine heart rate >130 beats per minute, persisting for at least 10 minutes. 
• Two (2) or more subjects who receive SOL-116 exhibit symptomatic bradycardia, 
defined as heart rate <40 beats per minute, or asymptomatic bradycardia, defined as 
resting supine heart rate <30 beats per minute while awake, persisting for at least 10 
minutes. 
• One (1) or more subjects who receive SOL-116 fulfills Hy’s law, defined as aspartate 
aminotransferase (AST) or alanine aminotransferase (ALT) ≥3 x upper limit of normal 
(ULN) and total bilirubin ≥2 x ULN, in the absence of a significant increase in alkaline 
phosphatase (ALP) and in the absence of an alternative diagnosis that explains the 
increase in total bilirubin (confirmed by repeating within 24 hours). 
• Two (2) or more subjects who receive SOL-116 exhibit ALT, total bilirubin, or ALP 
>3 x ULN accompanied by significant increase in other liver function test (confirmed 
by repeating within 24 hours). 
• Two (2) or more subjects who receive SOL-116 exhibit renal toxicity, defined as serum 
creatinine ≥1.5 x ULN (confirmed by repeating within 24 hours). 
• Two (2) or more subjects who receive SOL-116 exhibit hematologic toxicity, defined 
as one or more of the following (confirmed by repeating within 24 hours): 
o Leukocyte count <2.5 x 109/L 
o Neutrophil count <1.0 x 109/L 
o Platelet count <75 x 109/L 
In addition, the SRC may stop dose escalation at any time if the SRC determines that dose 
escalation would pose undue risk to subjects. If dose escalation is not stopped, the SRC may 
recommend ascending to the planned next-higher dose level cohort, ascending to a dose level 

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lower than the planned next-higher dose level cohort, or a repeat dosing at the current dose 
level. 
The safety and available PK data will be reviewed by the SRC. For the PK results, this will be 
done in a blinded manner (e.g., without subject identifiers or using reblinded subject numbers), 
but if the SRC considers it necessary due to a safety concern, individual subject data or an 
entire cohort’s data may be unblinded to the SRC to enable decision-making. Before any such 
unblinding, the reason for unblinding will be documented.  
SRC reports will be submitted to the IEC for approval of dose escalation. 
8.7.3 Re-initiation of Dose Escalation 
If dose escalation is terminated due to the criteria noted above, reduced and/or repeat dose 
levels (as allowed per protocol) may be administered to provide additional data regarding the 
frequency and/or severity of AEs. 
If the SRC agrees that these additional data suggest that the observations that initially resulted 
in a termination of dose escalation were not attributable to study medication, then dose 
escalation may be allowed to continue. 
8.8 Study Termination or Withdrawal of Subject/Patient from Study 
8.8.1 Study Termination 
If the Sponsor terminates or suspends the study, the Investigator or his/her designee should 
promptly inform the IEC (and/or regulatory authorities where required) of a temporary halt 
including the reason for such an action (see also Section 12.1.10). 
8.8.2 Subject/Patient Discontinuation or Withdrawal 
Subjects/patients may withdraw from the study at any time without prejudice to their future 
medical care by the physician or at the institution. Furthermore, a subject/patient may also be 
discontinued at any time should they meet the criteria defined in Section 12.1.9. 
The withdrawal of a subject/patient from the study should be discussed where possible with 
the Medical Monitor prior to withdrawal. If the subject is discontinued or withdraws from the 
study, the final evaluations are to be performed as completely as possible. 
8.8.3 Subject’s/Patient’s Follow-up after Study Discontinuation or Withdrawal 
The subjects/patients will be advised that participation in these investigations is voluntary. 
Furthermore, the subjects/patients may request that from the time point of withdrawal no more 
data will be recorded and that all biological samples collected during the study will be 
destroyed. 
In the case of premature discontinuation or withdrawal, the safety assessments scheduled for 
the EOS examination will be performed as soon as possible after study drug administration, as 
per Investigator judgement, unless the subject/patient withdrew informed consent. A safety 
follow-up visit will be performed as per Investigator judgement, unless the subject/patient 
withdrew informed consent. PK and PD assessments after early discontinuation will be 
performed upon mutual agreement between the Investigator and the Sponsor. 
8.8.4 Subject/Patient Replacement 
Drop-outs might be replaced but only upon mutual agreement between the Investigator and the 
Sponsor, unless withdrawal is due to a drug-related AE. The replacing subject/patient will 
receive the same treatment as assigned to the subject/patient whom he/she replaces. 

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Randomization will be performed by the Biostatistics department of QPS Qualitix Taiwan, 
according to Qualitix Taiwan SOPs. The randomization code and the randomization list will 
be generated using SAS version 9.4 or the last available version at time of randomization. 
The randomization code will be un-blinded and made available for data analysis only after 
study closure, i.e., when the study has been completed, the protocol deviations determined and 
the clinical database declared complete, accurate, and locked. 
8.10.3 Double-blinding 
The study is performed in a double-blind fashion. The Investigator and study staff (including 
processing lab personnel), the subjects/patients, the CRAs/monitors and the Sponsor’s staff 
will remain blinded to the treatment until study closure. The investigational drug and its 
matching placebo are indistinguishable. The labels of the syringes will be double blind and the 
packaging of the placebo/active syringes identical. Only after preparation of the syringe is 
completed, it will be handed over by pharmacy staff to the staff of the clinic. 
The randomization code will be kept strictly confidential. It is accessible only to the pharmacist 
on site, who is not involved in the conduct and analysis of the study, and will keep the 
randomization scheme strictly confidential. 
The bioanalytical laboratory will only analyze the samples of subjects/patients receiving SOL-
116, and not the samples of subjects/patients receiving placebo. Therefore, the bioanalytical 
laboratory will receive the randomization list from the biostatistician. The bioanalytical 
laboratory will not share this list with other parties and will blind all PK results before sending 
these to other team members. 
8.10.4 Emergency Procedure for Unblinding 
The Investigator receives emergency envelopes for each subject/patient containing the identity 
of the study drug dispensed. The Investigator and the study staff must remain blinded to the 
subject's/patient’s treatment assignment, even if the subject/patient refuses to participate in any 
study procedures or experiences an AE. The identity of the study drug may be revealed only if 
the subject/patient experiences a medical emergency whose management would be improved 
by the knowledge of the blinded treatment assignment. 
The occurrence of any code break during the study must be clearly justified and explained by 
the Investigator. Before opening the emergency envelope, every attempt must be made by the 
Investigator to discuss the intended code break with Lipum AB. In all cases, the Sponsor must 
be informed as soon as possible before or after the code break. 
Any code break must be documented on the emergency envelope and in a detailed report with 
the date and time of the code break and signed by the Investigator. This report is to be attached 
to the source documents and the date and time of code break will be documented in the eCRF. 
The CRA/monitor checks the emergency envelopes according to the Monitoring Plan (MP). 
8.11 Study Parameters 
8.11.1 Pharmacokinetic Parameters 
The serum PK parameters for SOL-116 will be derived by non-compartmental analysis of the 
serum concentration-time profiles. 
The following PK parameters have been defined: 
• Area under the concentration-time curve from time zero to infinity (AUC0-inf); 
• Maximum observed serum concentration (Cmax); 

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• Time to Cmax (Tmax); 
• AUC from time zero to time t of the last measured concentration above the limit of 
quantification (AUC0-t); 
• Terminal elimination half-life (T1/2); 
• Apparent volume of distribution (Vz/F); 
• Apparent total body clearance (CL/F). 
In multiple dosing part, Ctrough, time to steady state and accumulation ratio will also be assessed. 
Attainment of steady-state conditions will be determined by visual inspection of the pre-dose 
serum concentrations. 
8.11.1.1 Calculation of Pharmacokinetic Parameters and Assumptions 
The measured individual serum concentrations of SOL-116 will be used to directly obtain Cmax 
and Tmax. 
AUC0-t will be calculated according to the linear up/log down trapezoidal method using the 
measured concentration-time values above the lower limit of quantification (LLOQ). AUC0-inf 
will be calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value 
obtained by Ct/λ, where Ct is the last serum concentration measured above the LLOQ and λ 
represents the terminal elimination rate constant determined by log-linear regression analysis 
of the measured serum concentrations of the terminal elimination phase. The half-life of SOL-
116 will be calculated as follows: T1/2 = ln 2 / λ. 
The PK parameters will be based on actual blood sampling times [h] (relative to the 
corresponding administration time) rounded to two digits and negative pre-dose times will be 
set to zero. 
Please refer to Section 10 for more information on statistical methodology. 
8.11.2 Safety and Tolerability Parameters 
Baseline is defined as the last value measured prior to SOL-116 administration (vital signs, 
ECG, laboratory parameters), unless otherwise specified. 
The following parameters have been defined as parameters regarding safety and tolerability: 
• Clinical laboratory evaluations; 
• Injection site reactions; 
• AEs; 
• Immune reactions (e.g. hypersensitivity, cytokine release syndrome, immunogenicity); 
• Vital signs; 
• Physical examination; 
• ECGs (3-lead telemetry and 12-lead ECGs); 
• Concomitant medications/therapy. 
8.11.3 Immunogenicity Parameters 
The following are defined as immunogenicity parameters: 
• Development of ADA. If confirmed ADA positive, the following may be determined: 
o Estimation of ADA titers 
o Neutralizing capacity 
o Isotype 
o Epitope map 

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8.11.4 Exploratory Parameters 
The following are defined as exploratory parameters: 
• BSSL concentration; 
• Inflammatory biomarkers (except BSSL): CRP, ESR for all subjects/patients, and S-
calprotectin and hsCRP (only RA patients); 
• Cytokine/chemokine panel (including but not limited to IFNγ, IL-1β, IL-6, IL-10, IL-
12, IL-18, MCP-1 and TNFα); 
• Flow cytometry panel (only RA patients); 
• Whole blood stimulation assays (only RA patients). 

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9 SAFETY DEFINITIONS AND REPORTING REQUIREMENTS 
9.1 Adverse Events 
9.1.1 Definitions of Adverse Events 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product 
(International Council for Harmonization (ICH) E6; Section 1.2).  
A treatment-emergent AE is any AE temporally associated with the use of a study drug, 
whether or not considered related to the study drug. 
Adverse events include: 
• Exacerbation of a pre-existing disease. 
• Increase in frequency or intensity of a pre-existing episodic disease or medical 
condition. 
• Disease or medical condition detected or diagnosed after study drug administration 
even though it may have been present prior to the start of the study. 
• Continuous persistent disease or symptoms present at baseline that worsen following 
the start of the study. 
• Lack of efficacy in the acute treatment of a life-threatening disease. 
• Events considered by the Investigator to be related to study-mandated procedures.  
• Abnormal assessments, e.g., ECG, vital signs or physical examination findings, must 
be reported as AEs if they represent a clinically significant finding that was not present 
at baseline or worsened during the course of the study. 
• Laboratory test abnormalities must be reported as AEs if they represent a clinically 
significant finding, symptomatic or not, which was not present at baseline or worsened 
during the course of the study or led to dose reduction, interruption or permanent 
discontinuation of study drug. 
Adverse events do not include: 
• Medical or surgical procedure, e.g., surgery, endoscopy, tooth extraction, transfusion. 
However, the event leading to the procedure is an AE. If this event is serious, the 
procedure must be described in the SAE narrative. 
• Pre-existing disease or medical condition that does not worsen. 
• Situations in which an adverse change has not occurred, e.g., hospitalizations for 
cosmetic elective surgery or for social and/or convenience reasons. 
• Overdose of either study drug or concomitant medication without any signs or 
symptoms. However, overdose must be mentioned in the Study Drug Log. 
9.1.2 Intensity of Adverse Events 
The intensity of clinical AEs is graded on a three-point scale: mild, moderate, severe, and 
reported on specific AE pages of the eCRF. 
If the intensity of an AE worsens during study drug administration, the AE will be closed and 
a new AE with enhanced severity will be generated in the eCRF. If the AE lessens in intensity, 
no change in the severity is required. 

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If an AE occurs during a washout or placebo run-in phase and afterwards worsens during the 
treatment phase, a new AE page must be filled in with the intensity observed during study drug 
administration. 
Mild: Event may be noticeable to subject/patient; does not influence daily activities; usually 
does not require intervention. 
Moderate: Event may make subject/patient uncomfortable; performance of daily activities 
may be influenced; intervention may be needed. 
Severe: Event may cause noticeable discomfort; usually interferes with daily activities; 
subject/patient may not be able to continue in the study; treatment or intervention is usually 
needed. 
A mild, moderate or severe AE may or may not be serious. These terms are used to describe 
the intensity of a specific event (as in mild, moderate, or severe myocardial infarction). 
However, a severe event may be of relatively minor medical significance (such as severe 
headache) and is not necessarily serious. For example, nausea lasting several hours may be 
rated as severe, but may not be clinically serious. Fever of 39 °C that is not considered severe 
may become serious if it prolongs hospital discharge by a day (see Section 9.2.1.2). Seriousness 
rather than severity serves as a guide for defining regulatory reporting obligations. 
9.1.3 Relationship to Study Drug 
Adverse events should be assessed by the investigators as to whether or not there is a reasonable 
possibility of causal relationship to the study drug and reported as either related or unrelated. 
Related to study drug: This category applies to any AE (serious or not) that appears to have 
a reasonable possibility of causal relationship to the use of the study drug (i.e., a relationship 
cannot be ruled out). Guidelines to determine whether an event might be considered related 
include (but are not limited to) the following: 
• The event occurred in close temporal relationship to study drug administration. 
• The event abated (diminished) or disappeared when treatment with the study drug was 
down-titrated, interrupted, or discontinued. 
• The event re-occurred when treatment was re-introduced. 
• Environmental factors such as clinical state and other treatments could equally have 
caused the event. 
Related AEs should be considered as one of the following categories: 
Definite  
A clinical event, including laboratory test abnormality, occurring in a 
plausible time relationship to drug administration, and which cannot be 
explained by concurrent disease or other drugs or chemicals. The 
response to withdrawal of the drug (de-challenge) should be clinically 
plausible. The event must be definitive pharmacologically or 
phenomenologically, using a satisfactory re-challenge procedure if 
necessary.  
Probable 
A clinical event, including laboratory test abnormality, with a reasonable 
time sequence to administration of the drug, unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and which follows a 
clinically reasonable response on withdrawal (de-challenge). Re-
challenge information is not required to fulfill this definition.  
Possible  
A clinical event, including laboratory test abnormality, with a reasonable 
time sequence to administration of the drug, but which could also be 

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explained by concurrent disease or other drugs or chemicals. Information 
on drug withdrawal may be lacking or unclear.  
Unrelated to study drug: This category applies to any AE (serious or not) that does not appear 
to have a reasonable relationship to the use of study drug (see above guidelines). 
Unrelated AEs should be considered as one of the following categories: 
Unlikely  
A clinical event, including laboratory test abnormality, with a temporal 
relationship to drug administration which makes a causal relationship 
improbable, and in which other drugs, chemicals or underlying disease 
provide plausible explanations.  
Unrelated  
A clinical event, including laboratory test abnormality, which is clearly 
not related to drug administration.  
9.1.4 Reporting of Adverse Events 
All AEs occurring from the (first) dose administration and up to Follow-Up must be recorded 
on specific AE pages of the eCRF (note: only AEs for randomized subjects/patients will be 
recorded in the eCRF) see also Section 8.3.2.1. 
9.1.5 Follow-up of Adverse Events 
Adverse events must be followed until resolution, stabilization or up to EOS. Adverse events 
assessed as related must be followed until resolution, stabilization or to a maximum of 28 days 
after the EOS. 
9.2 Serious Adverse Events 
9.2.1 Definitions 
9.2.1.1 Serious Adverse Events 
A SAE is defined by the ICH guidelines as any AE fulfilling at least one of the following 
criteria: 
• Results in death. 
• Is life-threatening. Life-threatening refers to an event in which the subject/patient was 
at risk of death at the time of the event. It does not refer to an event that hypothetically 
might have caused death if it were more severe. 
• Requires subject’s/patient’s hospitalization or prolongation of existing hospitalization. 
• Results in persistent or significant disability or incapacity. 
• Is a congenital anomaly or birth defect. 
• Is medically significant or requires intervention to prevent at least one of the outcomes 
listed above. 
Important medical events that may not immediately result in death, be life-threatening, or 
require hospitalization may be considered as SAEs when, based upon appropriate medical 
judgment, they may jeopardize the subject/patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in the definitions above. 
The reference safety document to assess whether or not an SAE should be reported by the 
Sponsor to Health Authorities, IECs/institutional review boards (IRBs) and investigators in an 
expedited fashion is the Investigator’s Brochure. 

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9.2.1.2 Pregnancy 
All initial reports of pregnancy, including pregnancy outcome (follow-up) in female 
subjects/patients or in partners of male subjects/patients, must be reported to QPS safety unit 
(QPS SU) by the Investigator within 24 hours of his/her knowledge of the event using a 
Pregnancy Form.  
The Investigator will contact the subject/patient at the expected time of delivery for follow-up. 
Abnormal pregnancy outcomes (e.g., induced abortion, stillbirth, neonatal death, congenital 
abnormality, birth defect) are considered SAEs and must be reported using the Serious Adverse 
Event Form. 
9.2.1.3 Hospitalization – Prolongation of Existing Hospitalization 
Hospitalization is defined as an overnight stay in a hospital unit and/or emergency room. 
An additional overnight stay defines a prolongation of existing hospitalization. 
The following is not considered an SAE and should be reported as an AE only: 
• Treatment on an emergency or outpatient basis for an event not fulfilling the definition 
of seriousness given above and not resulting in hospitalization. 
The following reasons for hospitalizations are not considered AEs, and therefore not SAEs: 
• Hospitalizations for cosmetic elective surgery, social and/or convenience reasons. 
• Standard monitoring of a pre-existing disease or medical condition that did not worsen, 
e.g., hospitalization for coronary angiography in a patient with stable angina pectoris. 
• Elective treatment of a pre-existing disease or medical condition that did not worsen, 
e.g., hospitalization for chemotherapy for cancer, elective hip replacement for arthritis. 
9.2.1.4 Serious Adverse Events Related to Study-mandated Procedures 
Such SAEs are defined as SAEs that appear to have a reasonable possibility of causal 
relationship (i.e., a relationship cannot be ruled out) to study-mandated procedures (excluding 
administration of study drug) such as discontinuation of subject’s/patient’s previous treatment 
during a washout period, complication of a mandated invasive procedure (e.g., blood sampling, 
heart catheterization), car accident on the way to the hospital for a study visit, etc. 
9.2.2 Reporting of Serious Adverse Events  
9.2.2.1 Before Study Drug Initiation 
Serious adverse events occurring after signature of the Informed Consent and up to study drug 
initiation must be reported to the QPS SU. 
9.2.2.2 During Study Drug Administration 
All SAEs regardless of causal relationship must be reported, including those related to study-
mandated procedures. These SAEs occurring during study drug administration, i.e., between 
study drug initiation and EOS, are defined as treatment emergent SAEs. 
These SAEs are reported on SAE forms and also on AE pages in the eCRF. Therefore, they are 
entered both in the drug safety and clinical databases, and must be reconciled before study 
closure. 
9.2.2.3 After Study Drug Administration 
New SAEs, including those related to study-mandated procedures, occurring after study drug 
administration, i.e., until EOS, must be reported. 

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All SAEs occurring after study drug administration until Follow-Up must be recorded on an 
SAE form and as AEs in the eCRF. Therefore, these treatment-emergent SAEs are entered both 
in the QPS drug safety and clinical databases, and must be reconciled before study closure. 
9.2.2.4 Reporting Procedures 
All SAEs must be reported by a Principal Investigator to QPS SU within 24 hours of the 
Investigator’s knowledge of the event.  
All SAEs must be recorded on SAE forms, irrespective of the study drug received by the 
subject/patient, whether or not this event is considered by the Investigator to be related to study 
drug. 
These SAE forms must be sent to QPS SU. The Investigator must complete the SAE form in 
English (unless otherwise specified) and assess the relationship to study drug. 
Such preliminary reports will be followed by detailed descriptions that should include copies 
of hospital case reports, autopsy reports, hospital discharge summaries and other documents 
when requested and applicable. Follow-up information about a previously reported SAE must 
also be reported within 24 hours of receiving it. QPS SU may contact the Investigator to obtain 
further information. 
Suspected (considered related to the study drug) and Unexpected (not previously described in 
the reference safety information), Serious Adverse Reactions (SUSARs) will be expedited by 
QPS SU to Health Authorities, IEC/IRB and investigators, as appropriate. SUSARs will not be 
subject to systematic unblinding. 
9.2.3 Follow-up of Serious Adverse Events 
Serious adverse events still ongoing at the EOS visit must be followed until resolution or 
stabilization or until the event is otherwise explained or referral to appropriate medical care. 
New SAEs occurring at any time after the EOS or after the 28-day follow-up period after study 
drug discontinuation (whichever comes first) may be reported to QPS SU within 24 hours of 
the Investigator’s knowledge of the event, if felt appropriate by the investigators. 
Such information will only be entered into the drug safety database and hence will not affect 
study closure. 

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10 STATISTICAL METHODOLOGY AND ANALYSES 
10.1 Statistical Analysis Plan 
A statistical analysis plan (SAP) will be written and finalized before the study closure, i.e., 
database closure and unblinding of the randomization code of the study, if applicable. The SAP 
will provide full details of the analyses, the data displays and the algorithms to be used for data 
derivations. An SAP for safety and tolerability will be written by QPS Qualitix Taiwan. An 
SAP for the PK analyses (PKAP) will be written by QPS LLC. 
Any deviations from the original statistical plan will be described and justified in the final 
report. 
10.2 Analysis Sets 
Five different analysis sets are defined. Subjects/patients who withdraw from the study, or who 
have missing data, will be included in the statistical analyses provided that they are eligible for 
inclusion in the analysis population as described below. 
All-treated set: This analysis set includes all randomized subjects/patients who received study 
drug (at least one dose). 
Safety set: This analysis set includes subjects/patients from the All-treated set who had at least 
one safety assessment post-baseline. The safety set will be employed in the analysis of 
tolerability and safety variables.  
Immunogenicity set: This analysis set includes all subjects/patients who received the study 
treatment and had at least 1 post-dose immunogenicity sample collected. 
Per-protocol set: This analysis set comprises all subjects/patients included in the All-treated 
set who did not violate the protocol in a way that might affect the evaluation of the effect of 
the study drug(s) on the primary endpoint, i.e., without major protocol violations or deviations. 
The Per-protocol set will be employed in the analysis of PK and exploratory variables. 
PD (exploratory) set: This analysis set comprises all subjects/patients included in the All-
treated set who did not violate the protocol in a way that might significantly affect the ability 
to analyze exploratory endpoints (i.e. RA patients who received more than 2 intra-articular 
injections in large joints and/or 6 intra-articular injections in small joints during the study are 
excluded). 
10.2.1 Sample Size 
No formal sample size calculation has been performed. The proposed sample size is considered 
sufficient to provide adequate information for the study objectives. 
A statistical analysis plan will be prepared prior to database lock for each part of the study (see 
Section 10.1). 
10.2.2 Procedure for Accounting for Missing, Unused, and Spurious Data 
All analyses will be performed on data available at the time point considered. In summary 
tables, the number of subjects/patients with missing data will be presented unless otherwise 
specified. In calculation of percentages, subjects/patients with missing data will not be 
considered in numerator or denominator unless otherwise specified. 

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10.3 Pharmacokinetic Parameters 
The PK parameters will be calculated on the basis of the actual blood sampling time points. 
Please refer to Section 8.3.3.1 for details on the timing of sampling. 
10.3.1 Pharmacokinetic Statistical Analysis 
A definition of the PK parameters is described in Section 8.11.1. PK parameters will be 
described descriptively. 
The Per-protocol analysis set will be used for all PK analyses. Individual subject/patient listings 
will be provided. Mean and individual serum concentration-time profiles for SOL-116 will be 
presented graphically for each group. 
PK variables will be summarized using arithmetic mean, standard deviation, geometric mean, 
median, minimum, maximum, and coefficient of variation (CV%).  
Attainment of steady-state conditions will be determined by visual inspection of the pre-dose 
serum concentrations. 
10.4 Safety and Tolerability Parameters 
Definitions of the safety and tolerability parameters are described in Section 8.11.2. 
The safety set is used to perform all safety analyses. 
The medical history is coded using the latest version of MedDRA and listed. 
All AEs and SAEs are coded using the latest version of MedDRA. 
The treatment-emergent AEs are tabulated by system organ class (SOC), and individual 
preferred terms within each SOC by treatment group. The number and percentage of 
subjects/patients who experienced AEs coded with the same preferred term and SOC will be 
summarized by treatment group (in descending order according to the incidence in the 
investigational study drug group). Adverse events will also be tabulated by severity and by 
relationship to study drug. Summary tables will be accompanied by individual subject/patient 
listings broken down by treatment group, including pre-dose events. 
SAEs will be listed and summarized similarly to AEs. 
Reasons for death will only be listed. 
Reasons for premature discontinuation of study drug will be listed and summarized by 
frequency tables. 
ECG variables, vital sign measurements and laboratory measurements will be summarized at 
each time point using mean, median, standard deviation, min, max, number of available 
observations, and change from baseline. Individual subject/patient listings of physical 
examination data, ECG data, vital signs data, physical examination data, immune reactions, 
injection site reactions, concomitant medication/therapy and laboratory measurements will be 
provided. 
Standard numeric laboratory parameters are presented in the units supplied. If needed, a 
conversion will be made to standard units. 
10.5 Immunogenicity Parameters 
A definition of the immunogenicity parameters is described in Section 8.11.3. 

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Immunogenicity and exploratory parameters will be listed individually, displayed in 
appropriate graphics and summarized using descriptive statistics. 
10.6 Exposure to Study Drug 
A listing with information about the study drug administration will be provided. 
10.7 Baseline Parameters and Concomitant Medications 
Summary statistics (mean, median, standard deviation, min, max, number of available 
observations) will be provided for continuous demographic variables (e.g., age, height, weight). 
Individual subject/patient listings of demographic data will be provided. 
Qualitative demographic characteristics (gender, race) will be summarized by counts and 
percentages. Other baseline subject/patient characteristics (medical history, physical 
examination clinical findings, previous medications, inclusion/exclusion checklist) will only 
be listed.  
Distributions of these parameters will be compared between the treatment groups only 
descriptively. No statistical inference will be performed. 
Previous and concomitant medications will be coded according to the World Health 
Organization (WHO) drug code and the anatomic therapeutic chemical (ATC) class code. 
Concomitant medications will be summarized by tabulating the number and percentages of 
subjects/patients treated. 
10.8 Exploratory Analyses 
A definition of the exploratory parameters is described in Section 8.11.4. Exploratory 
parameters will be listed individually, displayed in appropriate graphics and summarized using 
descriptive statistics. The PD (exploratory) set will be used. Also, the PP set and the “all-treated 
set” will be used. 
Exploratory data-driven analyses can be performed with the caveat that any statistical inference 
will not have any confirmatory value. 
10.9 Interim Safety Report 
For Parts 1 and 2, the interim safety analysis will be conducted by the SRC on safety/tolerability 
and available PK data up to and including 14 days post-dose after completion of at least 6 
evaluable subjects per treatment group (subject assessed as pharmacokinetically evaluable at 
Day 14). For Part 3, the interim safety analysis will be conducted by the SRC on 
safety/tolerability and available PK data up to and including 28 days post last dose after 
completion of at least 6 evaluable subjects per treatment group (subject assessed as 
pharmacokinetically evaluable at Day 28 post last dose.  
Based on the results of the interim analysis (including but not limited to AEs, vital signs, ECGs, 
and clinical laboratory tests), a decision will be taken by the Principal Investigator(s) and 
Lipum AB whether the next cohort can start with the planned dose. This decision will only be 
made after discussion between the Principal Investigator(s) and the Sponsor and after mutual 
agreement and must be submitted to the IEC/IRB for approval before dosing can proceed. 

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10.10 Clinical Study Report 
Safety and tolerability parameters as well as PK and exploratory parameters (BSSL, CRP, 
hsCRP, ESR and S-calprotectin) will be evaluated in a Clinical Study Report. Certain 
exploratory parameters may be reported separately. 
 

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11 REFERENCES 
1. Debreova M, Culenova M, Smolinska V et al. Rheumatoid arthritis: From synovium 
biology to cell-based therapy. Cytotherapy 2022; 24:365-75. 
2. Tanski W, S’wiatoniowska-Lonc N, Tabin N et al. The Relationship between Fatty 
Acids and the Development, Course and Treatment of Rheumatoid Arthritis. Nutrients 
2022, 14, 1030. 
3. Nagy G, Roodenrijs NMT, Welsing PMJ et al. EULAR definition of difficult-to-treat 
rheumatoid arthritis. Ann Rheum Dis 2021; 80:31–35. 
4. Lindquist S, Hernell O. Lipid digestion and absorption in early life: an update. Curr 
Opin Clin Nutr Metab Care. 2010; 13:314-20. 
5. Lindquist S, Andersson E-L, Lundberg L, Hernell O. Bile salt-stimulated lipase plays 
an unexpected role in arthritis development in rodents. PLoS ONE 2012; 7(10): 
e47006.doi:10.1371/journal.pone.0047006). 
6. Investigators Brochure, edition 1.0, dated 08 August 2022. 
7. Lindquist S, Alenius G, Berntson L, et al. AB0132 A Novel Target for Treatment of 
Inflammatory Joint Diseases. Annals of the Rheumatic Diseases 2019;78:1525-1526. 
(abstract) 
8. Aletaha D, Neogi T, Alan J Silman AJ. Rheumatoid arthritis classification criteria: an 
American College of Rheumatology/European League Against Rheumatism 
collaborative 
initiative. 
Arthritis 
Rheum 
2010 
Sep;62(9):2569-81. 
doi: 
10.1002/art.27584. 
 
 

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12 PROCEDURES AND GOOD CLINICAL PRACTICE  
12.1 Procedures 
12.1.1 Protocol Amendments 
A change to a protocol has to be considered as an amendment as soon as these documents have 
been approved by IECs/IRBs or Health Authorities. The Sponsor is responsible to assess 
whether an amendment is substantial or non-substantial. Each amendment must be documented 
in writing by Lipum AB or its delegate. It should be reviewed by the Principal Investigator(s), 
Sponsor and other relevant team members, if appropriate. 
Adaptations of the core Subject Information and Informed Consent requested by IECs/IRBs 
are not considered as amendments, as long as they do not significantly change the core 
document or affect the protocol. 
12.1.1.1 Non-substantial Amendment 
Administrative or logistical minor changes require a non-substantial amendment. Such changes 
include but are not limited to changes in study staff or contact details (e.g., Lipum AB instead 
of CRO monitors) or minor changes in the packaging or labeling of study drug.  
The implementation of a non-substantial amendment could be done with or without (according 
to national regulations) notification to the appropriate IECs/IRBs and Health Authorities. It 
does not require their approval or to be signed by the investigators.  
12.1.1.2 Substantial Amendment 
Significant changes require a substantial amendment. Significant changes include but are not 
limited to: new data affecting the safety of subjects/patients, change of the objectives/ 
parameters of the study, eligibility criteria, dose regimen, study assessments/procedures, 
treatment or study duration, change of Principal Investigator or Sponsor’s legal representative, 
with or without the need to modify the core Subject Information and Informed Consent. 
Substantial amendments are to be approved by the appropriate IECs/IRBs and by the Health 
Authorities. The implementation of a substantial amendment can only occur after formal 
approval by the appropriate IECs/IRBs and/or Health Authorities and must be signed by the 
investigators. 
12.1.1.3 Urgent Amendment 
An urgent amendment might become necessary to preserve the safety of the subjects/patients 
included in the study. The requirements for approval should in no way prevent any immediate 
action being taken by the investigators or Lipum AB in the best interests of the 
subjects/patients. Therefore, if deemed necessary, an Investigator can implement an immediate 
change to the protocol for safety reasons. This means that, exceptionally, the implementation 
of urgent amendments will occur before submission to and approval by IECs/IRBs and Health 
Authorities.  
In such cases, the Investigator must notify Lipum AB within 24 hours. A related substantial 
amendment will be written within 10 working days by QPS Netherlands B.V. and submitted to 
the appropriate IECs/IRBs and Health Authorities. 
12.1.2 Site Monitoring 
Clinical site monitoring is conducted by the CRA/monitor to ensure that the rights and well-
being of human subjects are protected, that the reported study data are accurate, complete, and 

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verifiable, and that the conduct of the study is in compliance with the currently approved 
protocol/amendment(s), with ICH-GCP, SOPs and with applicable regulatory requirement(s). 
Details of clinical site monitoring are documented in a study specific MP. The MP describes 
includes a detailed description of:  
• the objectives and scope of monitoring,  
• the responsibilities of the CRA/monitor,  
• timelines of monitoring, 
• procedures (site initiation, interim monitoring visits, close out and protocol deviations),  
• at what level of detail monitoring will be performed, 
• communication and the distribution of monitoring reports. 
In general, an initiation visit will be performed before the first screening visit. Interim 
monitoring visits and contacts will occur at regular intervals thereafter, according to a 
frequency defined in the MP. A close-out visit will be performed after study closure. The 
Investigator is expected to be able to meet the CRA/monitor during these visits. The 
CRA/monitor will be available between visits if the Investigator or other staff needs 
information or advice. The CRA/monitor is to be informed by the Sponsor and/or Investigator 
about any relevant study updates as soon as possible. 
The Investigator will supply the Sponsor on request with any required background data from 
the study documentation or clinic records. This is particularly important when errors in data 
transcription are suspected. In case of special problems and/or governmental queries, it is also 
necessary to have access to the complete study records, provided that subject confidentiality is 
protected. 
The Investigator may convert study site visits to remote monitoring visits (telemedicine, 
telehealth, video presence or via other systems), with the approval of the Sponsor. 
12.1.3 Data Management 
12.1.3.1 Data Collection 
A Subject Screening and Enrollment Log will be completed for all eligible or non-eligible 
subjects/patients with the reasons for exclusion. 
Data will be collected according to local SOP of the clinic. 
For each randomized subject/patient, regardless of study drug initiation, an eCRF must be 
completed and signed by a Principal Investigator or sub-investigator. This also applies to 
randomized subjects/patients who fail to complete the study. If a subject/patient withdraws 
from the study, the reason must be noted on the eCRF. The eCRF is to be completed on an 
ongoing basis. Designated investigator staff will enter the data required by the protocol into 
the eCRF. Designated investigator site staff will not be given access to the electronic data 
capture system until they have been trained. The Investigator or sub-investigator must certify 
that the data entered into the eCRF are complete and accurate. 
12.1.3.2 Database Management and Quality Control 
After completion of the eCRF, each subject/patient will be electronically approved (signed) by 
the Investigator. 
The CRA/monitor will perform source data verification according to the MP and the SOPs of 
QPS Netherlands B.V. The CRA will use eCRF systems to track the monitoring queries and 
their resolution by the site.  

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All eCRF data will be validated by Data Management of QPS Netherlands B.V., according to 
specifications described in the Data Management Plan and the applicable SOPs. 
After the eCRF has been declared complete and accurate, the eCRF will be locked, after written 
approval of the Sponsor. Any changes to the eCRF after that time require a database unlock 
and can only be made after receipt of written approval of the Sponsor. 
12.1.4 Recording of Data and Retention of Documents 
The Investigator will maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents will 
be classified into two different categories: Investigator Site File (ISF), and subject/patient 
clinical source documents (electronic and/or paper). 
The ISF will contain the protocol/amendments, FDA form 1572 for studies conducted under a 
US IND, financial disclosure form, eCRFs, IEC/IRB and Health Authority approval with 
correspondence, informed consent, drug records, staff curriculum vitae and authorization 
forms, screening and enrolment logs, and other appropriate documents/correspondence as per 
ICH/GCP and local regulations. 
Subject/patient clinical source documents include, but are not limited to subject/patient 
hospital/clinic records, physician's and nurse's notes, original laboratory, ECG, X-ray, 
pathology and special assessment reports, consultant letters, etc. 
These two categories of documents must be kept on file by the Investigator for as long as 
needed to comply with national and international regulations (generally 2 years after 
discontinuing clinical development or after the last marketing approval). No study document 
should be destroyed without prior written approval from Lipum AB. Should the Investigator 
wish to assign the study records to another party, or move them to another location, Lipum AB 
must be notified in advance. 
When source documents are required for the continued care of the subject/patient, appropriate 
copies should be made for storing outside of the site. 
The handling of personal data will comply with the EU General Data Protection Regulation 
and the Dutch Act on Implementation of the General Data Protection Regulation. 
12.1.5 Audit 
Lipum AB’s quality assurance (QA) Manager or delegate may conduct audits of clinical 
research activities in accordance with internal SOPs to evaluate compliance with the principles 
of GCP and ICH related guidelines. 
Health Authorities may also wish to conduct an inspection (during the study or after its 
completion). Should an inspection be requested by Health Authorities, the Investigator must 
inform Lipum AB immediately that such request has been made. 
The Investigator will permit such audits by Lipum AB or Health Authorities and facilitate them 
by providing access to the relevant source documents. 
12.1.6 Handling of Study Drug(s) 
Lipum AB will supply all study drug(s) to the site according to local regulations. Drug supplies 
must be kept in an appropriate, secure area and stored according to the conditions specified on 
the drug labels. The site must maintain an accurate record of the shipment and dispensing of 
study drug(s) on an accountability form, which must be given to the monitor at the end of the 
study. An accurate record of the date and amount of study drug(s) dispensed to each 
subject/patient must be available for inspection at any time. 

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All drug supplies are to be used only for this protocol and not for any other purpose. The 
responsible person must not destroy any drug labels, or unused drug supply. Upon termination 
of the study, the monitor will collect used and unused drug subject/patient kits. They will be 
sent to the warehouse, where the Sponsor or its deputy will check drug accountability. In certain 
circumstances, used and unused drug containers can be destroyed at the site once drug 
accountability is final and checked by the Sponsor or its deputy and written permission for 
destruction has been obtained from Lipum AB. 
12.1.7 Publication of Study Results 
In accordance with standard editorial and ethical practice, Lipum AB will support publication 
of the data.  
12.1.8 Disclosure and Confidentiality 
By signing the protocol, the Investigator agrees to keep all information provided by Lipum AB 
in strict confidence and to request similar confidentiality from his/her staff and the IEC/IRB. 
Study documents provided by Lipum AB (e.g. investigators' brochures, protocols, eCRFs and 
other protocol-related documents) will be stored appropriately to ensure their confidentiality. 
The information provided by Lipum AB to the Investigator may not be disclosed to others 
without direct written authorization from Lipum AB, except to the extent necessary to obtain 
informed consent from subjects/patients who wish to participate in the study. 
12.1.9 Stopping rules for Subject/Patient 
Should a subject/patient experience an AE or SAE that meets the following criteria, the 
subject/patient may be immediately discontinued from the study: 
• Any AE or SAE in the judgement of the Investigator or subject/patient justifies 
withdrawal due to its severity, nature, or requirement for treatment, regardless of the 
causal relationship to the study drug. 
• Clinically relevant test procedure results which endanger the subject/patient.  
The reason(s) will have to be recorded on the appropriate page of the eCRF for each 
prematurely discontinued subject/patient. 
For discontinued subjects/patients, the assessments scheduled for the EOS examination will be 
performed as soon as possible after study drug administration. 
If the Sponsor terminates or suspends the study, the Investigator should promptly inform the 
IEC/IRF (and/or regulatory authorities where required) of a temporary halt including the reason 
for such an action. 
12.1.10 Premature Termination or Suspension of the Study 
Both Lipum AB and the Investigator reserve the right to terminate the study at any time. 
If a study is prematurely terminated or suspended, Lipum AB will promptly inform the 
investigators, the IECs/IRBs and Health Authorities, as appropriate, and provide the reason(s) 
for the termination or suspension. 
If the study is prematurely terminated or suspended for any reason, the Investigator in 
agreement with Lipum AB should promptly inform the enrolled subjects/patients and ensure 
their appropriate treatment and follow-up. 
In addition, if the Investigator terminates or suspends a study without prior agreement of the 
Sponsor, the Investigator should promptly inform Lipum AB and the IEC/IRB, and should 
provide the Sponsor and the IEC/IRB with a detailed written explanation of the termination or 
suspension. 

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If the IEC/IRB terminates or suspends its approval/favorable opinion of a study, the 
Investigator should promptly notify Lipum AB and provide Lipum AB with a detailed written 
explanation of the termination or suspension. 
12.2 Good Clinical Practice 
12.2.1 Ethics and Good Clinical Practice 
The Investigator will ensure that this study is conducted in full conformance with the principles 
of the "Declaration of Helsinki" (as amended in Tokyo, Venice, Hong Kong, Somerset-West, 
Edinburgh, Washington DC, Seoul and Fortaleza) and with the laws and regulations of the 
country in which the clinical research is conducted. 
All studies must follow the ICH/GCP Guidelines and, if applicable, the Code of Federal 
Regulations. 
12.2.2 Quality Control and Quality Assurance 
Quality control will be applied to each stage of data handling to ensure that all data are reliable 
and have been processed correctly. 
The Sponsor can decide to conduct an audit at the clinical study center. The audit will be 
conducted with the aim to ensure that the clinical study is performed and data are generated, 
documented (recorded) and reported in compliance with GCP and applicable regulatory 
requirements. An external party may be contracted for this purpose. 
On request of the Sponsor, the QA department may perform a study audit including the data 
management process. 
12.2.3 Independent Ethics Committee / Institutional Review Board 
The Investigator will submit this protocol and any related document provided to the 
subject/patient (such as subject/patient information used to obtain informed consent) to an IEC 
or IRB. Approval from the committee must be obtained before starting the study, and should 
be documented in a dated letter to the Investigator, clearly identifying the study, the documents 
reviewed and the date of approval. A list of members participating in the meeting must be 
provided, including the functions of these members. If study staff were present, it must be clear 
that none of these persons voted. 
Modifications made to the protocol after receipt of the IEC/IRB approval must also be 
submitted as amendments by the Investigator to the IEC/IRB in accordance with local 
procedures and regulations (see Section 12.1.1). 
12.2.4 Informed Consent and Recruitment 
It is the responsibility of the Investigator to obtain written informed consent from each 
individual participating in this study after adequate explanation of the aims, methods, and 
objectives of the study and potential hazards of the study drug. The Investigator must also 
explain to the subjects/patients that they are completely free to refuse to enter the study or to 
withdraw from it at any time for any reason. Appropriate forms for documenting written 
informed consent will be provided to the site prior to the study. 
The Informed Consent and Subject Information will be provided in English and/or the local 
language, as applicable. 
Healthy subjects will be recruited via social media channels. 
Patients will be recruited by referral from their treating rheumatologist.  

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12.2.5 Compensation to Subjects/Patients and Investigators 
Lipum AB is providing insurance in order to indemnify (legal and financial coverage) the 
Investigator/center against claims arising from the study, except for claims that arise from 
malpractice and/or negligence. 
The compensation of the subject/patient in the event of study-related injuries will comply with 
the applicable regulations. 

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13 STRUCTURED RISK ANALYSIS 
13.1 Potential Issues of Concern 
13.1.1 Level of Knowledge About Mechanism of Action 
 
 
 
 
 
 
 
 
 
 
 
 
13.1.2 Previous Exposure of Human Beings with the Test Product(s) and/or Products 
with a Similar Biological Mechanism 
First-in-human study, first-in-class drug, not applicable. 
13.1.3 Can the Primary or Secondary Mechanism be Induced in Animals and/or in Ex-
vivo Human Cell Material? 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol 
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13.1.4 Selectivity of the Mechanism to Target Tissue in Animals and/or Human Beings 
 
 
 
 
13.1.5 Analysis of Potential Effect 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
13.1.6 Pharmacokinetic Considerations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
13.1.7 Study Population 
Up to 48 healthy male and female volunteers, and 1 cohort of 8 RA patients will be enrolled, 
aged between 18-65 years. Females of childbearing potential may be enrolled if they agree to 
use appropriate contraception. 
13.1.8 Interaction with Other Products 
Metabolism and potential metabolic interactions have not been investigated. Based on the fact 
that both SOL-116 and its target BSSL being proteins, and since SOL-116 is not directly 
binding proinflammatory cytokines, there are no expected drug-drug interactions with small 
molecule drugs.  

QPS code: 210463-CS0382 
Clinical Study Protocol 
Sponsor code: LPM-116-001 05 August 2024, Amendment 6 
Template TSP820.01-4, effective date 01 May 2022 
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In the RA cohort, all patients will receive concomitant treatment with methotrexate (MTX). No 
pharmacodynamic interactions are expected as MTX affect the folic acid synthesis and SOL-
116 affects cells in the immune system. 
13.1.9 Predictability of Effect 
The PK behavior of SOL-116 in the preclinical studies appears predictable and in line with 
what is expected after s.c. injections of a monoclonal antibody. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
13.1.10 Can Effects be Managed? 
No antidote is available. Treatment of adverse effect will be symptomatic, tailored to the nature 
of the events. Subjects with a history or known hypersensitivity or allergy are excluded from 
participation in the study. There is also immediate access to equipment, qualified staff and an 
intensive care unit in case of an acute emergency.  
13.2 Synthesis 
This is a First-in-Human trial with a First-in-Class novel investigational medicinal product. 
Given the available nonclinical safety data, the selected starting dose and the oversight of dose 
escalation steps by a Safety Review Committee and ethics committee, the overall risk 
assessments are acceptable in these populations of healthy volunteers and RA patients, given 
the dose and the close supervision during the study. 
13.3 Category study 
Conclusions 
 
Based on the risk analysis the study can be 
performed without additional conditions. 
 
Based on the risk analysis the study can be 
performed with the following additional conditions: 
 
 
Based on the risk analysis the study cannot be 
performed. The main issue is: