This protocol was amended for the following reasons: 1. Changes to the Sponsor, Medical Monitor, PFT parameters; 2. To clarify: that participants with chronic medical issues may be at higher risk for serious illness from COVID-19, that participants who require high-resolution computed tomography (HRCT) scan during screening will have an additional one at Week 52, that reloading of 3 doses of PRM-151 would be required on the resumption of study treatment if a dose was missed, the use of pirfenidone or nintedanib treatment was permitted, that baseline serum concentration would be analyzed for all participants, that body weight should be measured at the start of each dosing period, administration of study drug could be permitted in other settings if participants couldn’t attend study site, that precautions are to be taken when performing pulmonary function tests, 6-MW test should be followed by other tests, what events were recorded as health care utilization, blood PAXgene was not applicable for Chinese participants enrolled in mainland China, participants should be followed up by telephone if they couldn’t attend the study site, that screening for infections prior to and during the study should be considered during a pandemic, the safety evaluable population, and the number of sites participating in the study; 3. Placebo was included as an IMP; 4.Updates to the permitted and prohibited therapy; 5.The sequence of assessments, pregnancy safety requirements, AE reporting period, efficacy and biomarker analyses were amended; 6. Medical history requirements were updated; 7. Oxygen saturation was included as part of vital sign measurements; 8. An independent, blinded Adjudication Committee was added; 9. SARS-CoV-2 serology testing was added as a lab assessment; 10. Serum sample for tryptase has been added in case of IRRs; 11.Clinically significant ECG abnormalities would be reported as AEs; 12. A statistician was added to the iDMC; 13. Appendices were updated.

This protocol was amended for the following reasons: 1) PK samples were to be collected as plasma instead of serum; 2) Clarification that lung biopsies should be submitted; 3) Clarification of the formulation of PRM-151; 4) Clarification that clarified that for loading or reloading doses, scheduled efficacy assessments would only be performed on the first of the three loading dose days; 5) Language was added to indicate that acceptability of the spirometry and diffusing capacity for carbon monoxide data was determined by over-readers blinded to study drug treatment; 6) Information regarding acute or suspected acute IPF exacerbation would no longer need to be recorded; 7) Serious hypersensitivity reactions and Grade 4 IRR or two Grade 3 IRRs were added as reasons for permanent study treatment discontinuation; 8) After the end of the AE reporting period, all deaths did not need to be reported on the eCRF; 9) Clarification regarding suspected and unsuspected SAEs reporting; 10) Additional details regarding iDMC reviews were added; 11) Appendices were amended.

This protocol was amended for the following reasons: 1) Additional text was added throughout the protocol to further clarify or explain information in more detail; 2) “Progression-free survival”was updated to “Time to disease progression” in secondary efficacy objective; 3) Exclusion criteria was updated; 4) Clarification of vital sign measurements at dosing visits; 5) Clarification that all past anti fibrotic therapy would be recorded; 6) Clarification that participants who had high-resolution computed tomography (HRCT) at screening received further HRCT imaging at Week 52; 7) Clarification that medical occurrences that began before the start of study treatment but after obtaining informed consent would be recorded on the electronic case report form (eCRF); 8) Clarification that DLCO assessments would be performed using local equipment; 9) Clarification that oxygen titration procedures would be conducted as per local standard of care; 10) Clarification that blood sample for a serum tryptase sample and complement C3 test would be collected at the time of a suspected anaphylaxis or hypersensitivity event whenever possible; 10) Additional information was provided on sample collection; 11) Assessments following hospitalization for COVID-19 would be collected and analysed; 12) The supplementary estimand was removed; 13) Clarification that an external global Steering Committee provided oversight of Studies WA42293 and WA42294; 14) The international non-proprietary name replaced the RO number throughout the protocol.