Phase 2 Active Treatment Study to Evaluate the Efficacy and Safety of SRK-015 in Patients With Later-Onset Spinal Muscular Atrophy (TOPAZ)
Phase: PHASE2
Conditions: Spinal Muscular Atrophy, Spinal Muscular Atrophy Type 3, Spinal Muscular Atrophy Type 2, SMA, Neuromuscular Diseases, Muscular Atrophy, Atrophy, Muscular Atrophy, Spinal, Neuromuscular Manifestations
Sponsor: Scholar Rock, Inc.

 
 
 
 
 
19 January 2022 
 
Clinicaltrials.gov Results Posting 
 
Re: SRK-015-002 Results from 12-Month Treatment Period 
 
Sponsor: 
Scholar Rock, Inc. 
301 Binney Street, 3rd Floor 
Cambridge, MA 02142 USA 
Protocol Number: 
SRK-015-002 
Protocol Title: 
Phase 2 Active Treatment Study To Evaluate The Efficacy And 
Safety of SRK-015 in Patients With Later-Onset Spinal Muscular 
Atrophy (TOPAZ) 
NCT Number: 
03921528 
Protocol Document 
Date: 
3 August 2021 
Statistical Analysis Plan 
Document Date: 
24 February 2021 
  
 
Thank you, 
Clinical Trial Coordinator 
Scholar Rock 
clinicaltrials@scholarrock.com 

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Page 1 
1.
TITLE PAGE
PROTOCOL SRK-015-002 
PHASE 2 ACTIVE TREATMENT STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF SRK-015 
IN PATIENTS WITH LATER-ONSET SPINAL 
MUSCULAR ATROPHY (TOPAZ) 
Protocol Number:  
Indication Studied: 
Developmental Phase of Study: 
IND Number: 
EudraCT Number 
Description: 
Sponsor: 
Sponsor Contact: 
Medical Monitor: 
Protocol Version: 
Release Date: 
SRK-015-002 
Spinal Muscular Atrophy 
2 
136872 
2018-004383-65 
Fully Human Anti-proMyostatin Monoclonal 
Antibody 
Scholar Rock, Inc. 
301 Binney Street, 3rd Floor 
Cambridge, MA 02142, USA 
 
5.0 
03 August 2021 
CONFIDENTIAL 
This document contains confidential information. Any use, distribution, or disclosure without the 
prior written consent of Scholar Rock is strictly prohibited except to the extent required under 
applicable laws or regulations. Persons to whom the information is disclosed must be informed 
that the information is confidential and may not be further disclosed by them.

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SPONSOR SIGNATURE 
I have read and approve this protocol. My signature, in conjunction with the signature of the 
Principal Investigator, confirms the agreement of both parties that the clinical study will be 
conducted in accordance with the protocol and all applicable laws and regulations, including, but 
not limited to, the International Council for Harmonisation (ICH) Guideline for Good Clinical 
Practice (GCP), the Code of Federal Regulations (CFR), and the ethical principles that have their 
origins in the Declaration of Helsinki. 
George Nomikos, MD, PhD 
SVP, Medical & Clinical Research 
Head of Muscle Therapeutic Area 
Scholar Rock, Inc. 
Date 
mikos, MD, PhD
calalalalalalalalalalalalal & Clinical Research
l Th
i A

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PRINCIPAL INVESTIGATOR’S AGREEMENT 
 
I have read and approve this protocol. My signature, in conjunction with the signature of the 
Sponsor, confirms the agreement of both parties that the clinical study will be conducted in 
accordance with the protocol and all applicable laws and regulations, including, but not limited 
to, the ICH Guideline for GCP, the CFR, and the ethical principles that have their origins in the 
Declaration of Helsinki. 
Nothing in this document is intended to limit the authority of a physician to provide emergency 
medical care under applicable regulations. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Principal Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Principal Investigator 
 
 
 
 
 
 
 
 
Date 
 

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1. 
SYNOPSIS 
Name of Sponsor: 
Scholar Rock, Inc., 301 Binney Street, 3rd Floor, Cambridge, MA 02142, USA 
Name of Investigational Product: 
apitegromab (SRK-015)  
Name of Active Ingredient: 
apitegromab 
Protocol Number: 
SRK-015-002 
Title of Study: Phase 2 Active Treatment Study to Evaluate the Efficacy and Safety of SRK-015 in 
Patients with Later-onset Spinal Muscular Atrophy (TOPAZ) 
Study Centers: 
Approximately 20 study sites across the United States (US) and Europe 
Phase of Development: 2 
Objectives for Both the Treatment Period and Extension Periods: 
Primary Objectives: 
• 
To assess safety and tolerability of SRK-015 in patients with later-onset (e.g., Type 2 and 
Type 3) spinal muscular atrophy (SMA) 
• 
To assess the efficacy of SRK-015 by assessing changes in motor function outcome measures 
in 3 separate predefined cohorts 
Secondary Objectives: 
• 
To characterize the pharmacokinetics (PK) of SRK-015 
• 
To evaluate the pharmacodynamic (PD) effects of SRK-015 
• 
To evaluate time to therapeutic effect between low- and high-dose SRK-015 in a predefined 
cohort (Cohort 3) 
• 
To evaluate the immunogenicity of SRK-015 
• 
To evaluate the effect of SRK-015 on quality of life  
Methodology: 
This study will be conducted in approximately 20 study sites across the US and Europe to evaluate the 
safety and efficacy of SRK-015 in patients with later-onset SMA (e.g., patients with Type 2 and Type 3 
SMA) age 2 through 21 years old. Patients may receive SRK-015 on top of an approved SMA 
treatment or may receive SRK-015 as monotherapy. Approximately 55 male and female patients with 
later-onset SMA will be enrolled across 3 separate parallel subpopulations subsequently described as 
cohorts. Patients will receive SRK-015 every 4 weeks during the 52-week Treatment Period, with 
patients in Cohorts 1 and 2 directly assigned high-dose (20 mg/kg) SRK-015 and patients in Cohort 3 
randomized 1:1 double-blind between low-dose (2 mg/kg) and high-dose (20 mg/kg) SRK-015. 

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• 
Cohort 1, N=20: Ambulatory Type 3 patients, age 5 through 21 years old, approximately 10 of 
whom are not receiving an approved SMA treatment, as well as patients already receiving an 
approved SMA treatment that had been started after the patient turned 5 years old. 
• 
Cohort 2, N=15: Type 2 and nonambulatory Type 3 patients, age 5 through 21 years old, 
already receiving an approved SMA treatment that had been started after the patient turned 
5 years old. 
• 
Cohort 3, N=20: Type 2 patients, age ≥2 years old, already receiving an approved SMA 
treatment that had been started before the patient turned 5 years old. 
During the Screening Period, all patient screening and eligibility determinations will be conducted after 
informed consent (and, as required by local authorities, patient informed assent) has been provided and 
within 28 days prior to first dose. Screening motor function outcome measures will be conducted at 
least 7 days prior to the first dose. All subsequent motor function outcome measures will be conducted 
within 96 hours prior to dosing. 
During the Treatment Period, patients will be monitored at the study site through 2 hours postdose. 
Following each Treatment Period dose, patients will be contacted by the site within 7 days for a safety 
check-in-. Patients will be seen in clinic 14 days after the first Treatment Period dose. After the second 
dose, visits will occur every 4 weeks through the end of the study (Study Schedule of Assessments). 
Patients who complete the 52-week Treatment Period will have the option to enroll into an Extension 
Period (referred to as Extension Period A), for an additional 52-week period. There will be no 
interruption in dosing between the completion of the Treatment Period and the start of Extension 
Period A. Patients who consent to participate in Extension Period A will complete both the Treatment 
Period Day 364 (V15) visit and the Extension Period A Day 364 (E1) visit on the same day. 
Based on the results of the prespecified 6-month safety and efficacy interim analyses, any Cohort 3 
patients who were randomized to receive low-dose (2 mg/kg) SRK-015 will be re-assigned to receive 
high-dose (20 mg/kg) SRK-015 after completion of the Treatment Period. Due to the variability in 
timing of regulatory authority and/or Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approvals, the timepoint at which patients who received the low dose (2 mg/kg) will begin 
receiving the high dose (20 mg/kg) during Extension Period A will vary. 
Patients who complete the 52-week Treatment Period and choose not to enroll into Extension Period A 
will be followed for a 12-week Safety Follow-up Period after Day 364 (V15). 
Patients who complete Extension Period A will have the option to enroll into Extension Period B for an 
additional 52-week period. There will be no interruption in dosing between the completion of 
Extension Period A and the start of Extension Period B. Patients who consent to participate in 
Extension Period B will complete both the Extension Period A, Day 728 (E14) visit and the Extension 
Period B Day 728 (EB1) visit on the same day. 
Patients who complete Extension Period A and choose not to enroll into Extension Period B will be 
followed for a 12-week Safety Follow-up Period after Day 728 (E14). 
Patients who complete the 52-week Extension Period B will have the option to enroll into Extension 
Period C for an additional 52-week period. There will be no interruption in dosing between the 
completion of Extension Period B and the start of Extension Period C. Patients who consent to 
participate in Extension Period C will complete both the Extension Period B, Day 1092 (EB14) visit 
and the Extension Period C Day 1092 (EC1) visit on the same day. 
Patients who complete Extension Period B and choose not to enroll into Extension Period C will be 
followed for a 12-week Safety Follow-up Period after Day 1092 (EB14). 
Patients who complete the 52-week Extension Period C may be offered the option to enter a separate 
long-term safety extension trial at that time. Patients who complete the 52-week Extension Period C 

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and choose not to enroll in the separate long-term safety extension trial will be followed for a 12-week 
Safety Follow-up Period after Day 1456 (EC14). 
Patients will be monitored throughout the Treatment Period, Extension Periods A, B, and C, and the 
Follow-up Period for safety. A safety surveillance team (SST) will review safety data throughout the 
duration of the study to assess patient safety. The SST will review safety data approximately every 
6 months. Prior to Protocol Version 5.0, the SST review was approximately every 12 weeks. The SST 
will be blinded to all cohort-level efficacy outcomes through the completion of the predefined safety 
and efficacy interim analysis, and to all individual efficacy outcomes through the completion of the 
52-week Treatment Period analysis. If a significant safety signal emerges at any time during the study, 
dosing may be suspended until the SST can evaluate the signal, recommend an appropriate course of 
action, and ensure the ongoing safety of all patients. 
Study Stopping Rules: Dosing in the study may be suspended at any time for an emergent safety 
concern by the Medical Monitor in consultation with the SST until the SST can completely evaluate the 
event(s) and recommend an appropriate course of action. The Sponsor may terminate the study if it 
determines that further drug exposure would pose an undue risk to patients. The Sponsor, at its 
discretion, may terminate the study at any time. 
If the study is terminated prematurely, Investigators, regulatory authorities, and IRBs/ IECs will be 
notified promptly. Patients will continue to be followed for 12 weeks after their final dose. 
Individual Stopping Rules: Dosing for any individual patient may be suspended or discontinued if the 
patient experiences a serious adverse event (SAE) related to SRK-015 or a clinically significant 
nonserious adverse event (AE) related to SRK-015 that, in the assessment of the Investigator and in 
consultation with the Medical Monitor, warrants suspension or discontinuation from further dosing for 
that patient’s well-being. For patients who have had their dosing suspended, dosing may resume only 
after their AE has resolved and only if it would be considered safe to do so in the assessment of the 
Investigator (and in consultation with the Medical Monitor). For patients who have discontinued 
dosing, the patient will continue to be followed for 12 weeks after their final dose or until the 
resolution of any ongoing clinically significant AE, whichever occurs later. (For the definition of AE 
resolution, please refer to Section 10.7.1.2 Follow-up Reports.) 
Dosing of SRK-015 for an individual patient may also be suspended or discontinued for safety 
concerns other than those described above based on review by the SST or at the discretion of the 
Investigator if he/she feels the patient’s safety may be threatened. The Investigator may ask for an ad 
hoc SST meeting to be held for any single event or combination of events that in his/her professional 
opinion may jeopardize the safety of the patient or the reliability of the data. 
Criteria for Inclusion: 
1. Age 5 through 21 years old at the time of Screening for Cohorts 1 and 2; Age ≥2 years old at 
the time of Screening for Cohort 3 
2. Estimated life expectancy >2 years from Screening 
3. Informed consent document signed by the patient if the patient is legally an adult. If the patient 
is legally a minor, informed consent document signed by the patient’s parent or legal guardian 
and patient’s oral or written assent obtained, if applicable and in accordance with the 
regulatory and legal requirements of the participating location 
4. Documented diagnosis of 5q SMA 
5. Diagnosed as later-onset (e.g., Type 2 or Type 3) SMA prior to receiving any treatment with 
therapy approved for SMA 
6. Nonambulatory patients must be able to sit independently (sits up straight with head erect for 
at least 10 seconds; does not use arms or hands to balance body or support position) per World 

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Health Organization (WHO) motor milestones definition at Screening. Patients who never had 
the ability to walk independently will be classified as Type 2. Patients who previously had the 
ability to walk unaided will be classified as Type 3. 
7. Ambulatory patients must have the ability to independently ambulate without aids or orthotics 
over 10 meters at Screening 
8. For Cohort 1, Revised Hammersmith Scale (RHS) score no greater than 63 at Screening 
9. For Cohorts 2 and 3, Hammersmith Functional Motor Scale Expanded (HFMSE) score no less 
than 10 at Screening 
10. Receiving the same background SMA therapy (e.g., on an approved survival motor neuron 
(SMN) upregulator therapy such as nusinersen, or not on any SMA therapy) for at least 
6 months prior to Screening and anticipated to remain on that therapy throughout the duration 
of the study 
a. If receiving the SMN upregulator therapy nusinersen, must have completed the loading 
regimen and initiated maintenance dosing (i.e., completed at least one maintenance dose) 
with at least 4 weeks after the first maintenance dose having elapsed prior to Screening 
11. Nutritional status stable over the past 6 months and anticipated to be stable throughout the 
duration of the study 
12. Have no physical limitations that would prevent the patient from undergoing motor function 
outcome measures throughout the duration of the study 
13. Able to receive study drug infusions and provide blood samples through the use of a peripheral 
intravenous (IV) or a long-term IV access device that the patient has placed for reasons 
independent from the study (i.e., for background medical care and not for the purpose of 
receiving SRK-015 in the study), throughout the duration of the study 
14. Able to adhere to the requirements of the protocol, including travel to the study center and 
completing all study procedures and study visits 
15. For patients who are expected to have reached reproductive maturity by the end of the study, 
adhere to study-specific contraception requirements 
a. Females of childbearing potential (see Section 10.1.7.4 for definition) must have a negative 
pregnancy test at Screening and agree to employ highly effective contraceptive measures 
(failure rate of 1% or less per year when used consistently and correctly) for the duration 
of the study and for 18 weeks following the last dose of study drug. Effective 
contraception methods are restricted to combined (estrogen and progestogen containing) 
hormonal contraception associated with inhibition of ovulation (oral, intravaginal, 
transdermal), progestogen-only hormonal contraception associated with inhibition of 
ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-
releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence. In 
the context of this guidance, sexual abstinence is considered a highly effective method 
only if defined as refraining from heterosexual intercourse during the entire period of risk 
associated with the study treatments. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle 
of the patient. 
b. Male patients with female partners of childbearing potential must be abstinent or agree to 
employ the use of a condom with or without spermicide throughout the duration of the 
study and for 18 weeks following the last dose of study drug. 
 

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Criteria for Exclusion: 
1. Use of tracheostomy with positive pressure 
2. Use of chronic daytime noninvasive ventilatory support for >16 hours daily in the 2 weeks 
prior to dosing, or anticipated to regularly receive such daytime ventilator support chronically 
over the duration of the study 
3. Any acute or comorbid condition interfering with the well-being of the patient within 14 days 
of Screening, including active systemic infection, the need for acute treatment or inpatient 
observation due to any reason 
4. Severe scoliosis and/or contractures at Screening. Based on clinical judgment, any scoliosis or 
contractures present must be stable over the past 6 months, anticipated to be stable for the 
duration of the study and not prevent the patient from being evaluated on any functional 
outcome measures throughout the duration of the study. 
5. Pregnant or breastfeeding 
6. Major orthopedic or other interventional procedure, including spine or hip surgery, considered 
to have the potential to substantially limit the ability of the patient to be evaluated on any 
functional outcome measures, within 6 months prior to Screening, or anticipated for the 
duration of the study 
7. Prior history of a hypersensitivity reaction to a monoclonal antibody (mAb) or recombinant 
protein bearing an Fc domain (such as a soluble receptor-Fc fusion protein), SRK-015, or 
excipients of SRK-015 
8. Use of systemic corticosteroids within 60 days prior to Screening. Inhaled or topical steroids 
are allowed. 
9. Treatment with investigational drugs within 3 months or 5 half-lives, whichever is longer prior 
to Screening. 
10. Use of therapies with potentially significant muscle effects (such as androgens, insulin-like 
growth factor, growth hormone, systemic beta-agonist, botulinum toxin, or muscle relaxants or 
muscle-enhancing supplements) or potentially significant neuromuscular effects (such as 
acetylcholinesterase inhibitors) other than approved SMN upregulator therapy within 60 days 
prior to Screening. 
11. Use of valproic acid within 60 days prior to Screening. 
12. Patient has any other condition, which in the opinion of the Investigator may compromise 
safety or compliance, would preclude the patient from successful completion of the study, or 
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Investigational Product, Dosage, and Mode of Administration: SRK-015 is a clear to slightly 
opalescent, colorless to slightly yellow solution, essentially free from visible particulates, containing 
50 ± 5 mg/mL human anti-proMyostatin mAb protein in 20 mM histidine, 130 mM sodium chloride, 
and 0.02% polysorbate 80, pH 6.0 in 1-mL solution. SRK-015 drug product is stored in a 6R clear, 
USP/EP Type I borosilicate glass vial with a 20 mm Flurotec®-coated, bromobutyl or chlorobutyl 
rubber stopper and 20 mm crimp seal with a flip-off cap. Each vial is filled to allow for a 3 mL 
withdrawal. 
High-dose SRK-015 will be 20 mg/kg and low-dose SRK-015 will be 2 mg/kg. Doses will be diluted in 
normal saline and administered via IV over 2 hours +10-minute window. 
All doses will be administered via peripheral IV (or via long-term IV access device such as 
peripherally inserted central catheter or port, if the patient has such a device for their background 
medical care). The placement of a new long-term IV access device is not part of this study, not required 
for participation, and should not be conducted if the only reason for it is to receive SRK-015. If there 
are no acute reactions following the first 2 doses for a patient, and if the Investigator determines that it 
would be safe to do so, the infusion duration can be changed to less than 2 hours but no shorter than 
1 hour.  
Duration of Treatment: 
Treatment Period: 
Total study participation for an individual patient will consist of approximately 4 weeks for Screening, 
52 weeks of study visits, and, if the patient does not enroll into Extension Period A, 12 weeks of Safety 
Follow-up for a total duration of approximately 68 weeks (approximately 16 months). 
Extension Period A: 
Total study participation for an individual patient who completes both the Treatment Period and 
Extension Period A will consist of approximately 4 weeks for Screening, 104 weeks of study visits, 
and 12 weeks of Safety Follow-up for a total duration of approximately 120 weeks (approximately 
28 months). 
Extension Period B: 
Total study participation for an individual patient who completes the Treatment Period and Extension 
Periods A and B will consist of approximately 4 weeks for Screening, 156 weeks of study visits, and 
12 weeks of Safety Follow-up for a total duration of approximately 172 weeks (approximately 
40 months). 
Extension Period C: 
Total study participation for an individual patient who completes the Treatment Period and Extension 
Periods A, B, and C will consist of approximately 4 weeks for Screening, 208 weeks of study visits, 
and 12 weeks of Safety Follow-up for a total duration of approximately 224 weeks (approximately 
52 months). 
Reference Therapy, Dosage, and Mode of Administration: Not applicable 
Concomitant Treatments: 
Use of the following treatments will not be permitted during the study: 
• 
Live vaccinations within 14 days of any study visit where motor function outcome measures 
are conducted 
• 
Systemic corticosteroids. Inhaled and topical steroids are allowed. 
• 
Any therapy with potentially significant muscle effects (such as androgens, insulin-like growth 
factor, growth hormone, systemic beta-agonist, botulinum toxin, muscle relaxants, or muscle-

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enhancing supplements) or potentially significant neuromuscular effects (such as 
acetylcholinesterase inhibitors) other than approved SMN upregulator therapy 
• 
Valproic acid 
SRK-015 may be administered at least 24 hours prior to a maintenance dose of nusinersen and at least 
14 days after a maintenance dose of nusinersen. The dosing schedule for SRK-015, including 
maintaining acceptable visit windows, must be adhered to throughout the duration of the study. 
Criteria for Evaluation: 
Efficacy: 
Cohort 1: Ambulatory Type 3 Patients 
Primary Efficacy Endpoint: 
• 
Change from Baseline in the RHS total score at Day 364 (Visit 15) 
Secondary Efficacy Endpoints: 
• 
Change from Baseline in the RHS total score at other prespecified timepoints 
• 
Proportion of patients achieving various magnitudes of change in RHS score from Baseline 
• 
Change from Baseline in 6-Minute Walk Test (6MWT) 
• 
Change from Baseline in 30-Second Sit-to-Stand 
• 
Change from Baseline in 10-Meter Walk/Run (from the RHS) 
• 
Change from Baseline in timed rise from floor (from the RHS) 
Tertiary Endpoints: 
• 
Change from Baseline in Pediatric Evaluation of Disability Inventory Computer Adaptive Test 
(PEDI-CAT) 
• 
Change from Baseline in Patient-reported Outcomes Measurement Information System 
(PROMIS) Fatigue Questionnaire 
Cohort 2 and Cohort 3: Type 2 and Nonambulatory Type 3 Patients 
Primary Efficacy Endpoint: 
• 
Change from Baseline in HFMSE total score at Day 364 (Visit15) 
Secondary Efficacy Endpoints: 
• 
Change from Baseline in HFMSE total score at other prespecified timepoints 
• 
Proportion of patients achieving various magnitudes of change in HFMSE score from Baseline 
• 
Change from Baseline in Revised Upper Limb Module (RULM) total score 
• 
Change from Baseline in number of WHO motor development milestones attained 
• 
Proportion of patients achieving various magnitudes of change in RULM score from Baseline 
• 
Proportion of patients who attain a new WHO motor development milestone relative to 
Baseline 
Tertiary Endpoints: 
• 
Change from Baseline in Time to limitation on Endurance Shuttle Nine Hole Peg Test 
(ESNHPT) or Endurance Shuttle Box and Block Test (ESBBT) 
• 
Change from Baseline in PEDI-CAT 
• 
Change from Baseline in PROMIS Fatigue Questionnaire 

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Additional Tertiary Endpoint for Cohort 3: 
• 
Time to therapeutic effect (described in the statistical analysis plan [SAP]) as compared 
between low- and high-dose SRK-015 arms 
Safety: 
Safety will be evaluated based on occurrence of or changes in the following parameters: 
• 
Treatment-emergent adverse events (TEAEs) and SAEs 
• 
Vital signs, including blood pressure, heart rate, body temperature, and respiratory rate 
• 
Height and weight 
• 
Physical examinations 
• 
Laboratory assessments (hematology, serum chemistry, coagulation, urinalysis) 
• 
12-lead electrocardiogram (ECG) 
• 
Concomitant medications 
Safety assessments may be revised if any important safety signals emerge from any ongoing clinical 
studies (including this study). 
Pharmacokinetics, Pharmacodynamics, and Immunogenicity: 
Blood samples for the measurement of SRK-015 concentrations, circulating latent myostatin 
concentrations, and anti-SRK-015 antibodies will be obtained prior to dosing on Day 0 and throughout 
the Treatment and Extension Periods as well as the Safety Follow-up Period as indicated in the Study 
Schedule of Assessments. 
Sample Size Rationale: 
Sample sizes for each cohort were based on practical considerations. Sample sizes for Cohorts 1 (n=20) 
and Cohort 2 (n=15) each provide 80% power to reject the null hypothesis (expressed as means) 
relative to prespecified alternative hypothesis using a paired t-test with two-sided 5% Type 1 error for 
the mean change from Baseline for predefined cohort-specific primary efficacy endpoints. For Cohort 3 
(n=20), the effect size to compare dose groups is also justified for detection with 80% power and 
two-sided 5% Type I error for a 1:1 randomization (high dose versus low dose) as well as the 
treatment-specific effect sizes that will reject the null hypothesis of no mean difference according to 
two-sided testing for a predefined primary efficacy endpoint.  
Statistical Methods: 
Safety and efficacy endpoints will be separately analyzed by cohorts and within Cohort 3, by dose 
groups. The safety and efficacy endpoints will also be analyzed for different cohort/dose combinations 
taking cohort, dose level and receiving background SMA therapy into consideration. Any changes in 
the analysis as specified in the protocol will be delineated in the SAP. 
Vital signs and laboratory outcomes will be summarized within each treatment group within all cohorts 
and the 2 dose groups within Cohort 3. The incidence rate of AEs and TEAEs will be reported. 
The primary efficacy endpoints will be summarized within cohorts. In addition to the primary efficacy 
endpoint, there are multiple secondary efficacy endpoints to help characterize the multi-dimensional 
aspects of each cohort and to plan subsequent clinical studies in support of approval. All continuous 
endpoints will be summarized within cohorts; corresponding two-sided 95% confidence intervals will 
be computed. 
A prespecified interim analysis to evaluate the initial drug exposure (i.e., PK) and target engagement 
(i.e., PD) will be conducted. For Cohorts 1 and 2, this analysis will be conducted after approximately 
4 patients in a cohort have received at least 2 doses of SRK-015. For Cohort 3, this analysis will be 

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conducted after approximately 6 patients have received at least 2 doses of SRK-015. Data from 
multiple cohorts may be combined as necessary. Based on the interim analysis results, and taking into 
consideration any available safety data, cohort-specific dose levels may be adjusted. Any adjustment in 
dose level will not change the frequency of dosing (i.e., every 4 weeks) and the highest dose will not 
exceed 30 mg/kg, as tested in the Phase 1 study. 
Additionally, prespecified cohort-specific interim analyses to evaluate the initial safety and efficacy of 
SRK-015 in patients with SMA will be conducted after all patients complete Day 168 (Visit 8) or are 
terminated from the study. Interim analyses will be performed on the efficacy endpoints in addition to 
all safety outcomes and available PK and PD results. Safety data at all visits and efficacy endpoints at 
Day 168 (Visit 8) will be included in this analysis. 
 

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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
SPONSOR SIGNATURE ................................................................................................................2 
PRINCIPAL INVESTIGATOR’S AGREEMENT .........................................................................3 
1. 
SYNOPSIS ...................................................................................................................4 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............13 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................18 
4. 
INTRODUCTION ......................................................................................................20 
4.1. 
SRK-015 .....................................................................................................................20 
4.2. 
Spinal Muscular Atrophy ............................................................................................20 
4.3. 
Current Therapies and Unmet Medical Need .............................................................21 
4.4. 
Safety Rationale for SRK-015 ....................................................................................22 
4.5. 
Therapeutic Rationale for SRK-015 ...........................................................................23 
4.6. 
Study Rationale ...........................................................................................................23 
4.7. 
Dose Rationale ............................................................................................................24 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................26 
5.1. 
Primary Objectives for Both the Treatment Period and Extension Periods ...............26 
5.2. 
Secondary Objectives for Both the Treatment Period and Extension Periods ...........26 
6. 
INVESTIGATIONAL PLAN .....................................................................................27 
6.1. 
Overall Study Design ..................................................................................................27 
6.2. 
Treatment Assignment ................................................................................................29 
6.3. 
Safety Oversight and Stopping Rules .........................................................................40 
6.3.1. 
Safety Surveillance Team ...........................................................................................40 
6.3.2. 
Pharmacokinetic Criteria for Dose Adjustment ..........................................................40 
6.3.3. 
Study Stopping Rules .................................................................................................41 
6.3.4. 
Individual Stopping Rules ..........................................................................................41 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................42 
7.1. 
Patient Inclusion Criteria ............................................................................................42 
7.2. 
Patient Exclusion Criteria ...........................................................................................43 
7.3. 
Patient Withdrawal Criteria ........................................................................................44 

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7.4. 
Patient Rescreening, Replacement, and Over-enrollment ..........................................44 
7.5. 
Patient Enrollment into the Optional Extension Periods ............................................45 
8. 
STUDY TREATMENT ..............................................................................................46 
8.1. 
Study Drug Description ..............................................................................................46 
8.2. 
Study Drug Preparation and Administration ..............................................................46 
8.3. 
Randomization and Blinding ......................................................................................46 
8.4. 
Study Drug Compliance .............................................................................................47 
8.5. 
Study Drug Packaging and Labeling ..........................................................................47 
8.6. 
Study Drug Storage and Accountability .....................................................................47 
8.7. 
Study Drug Disposal and Return ................................................................................47 
8.8. 
Concomitant Treatment ..............................................................................................48 
9. 
ASSESSMENT OF EFFICACY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS ........................................................................................49 
9.1. 
Efficacy Endpoints ......................................................................................................49 
9.1.1. 
Efficacy Parameters ....................................................................................................50 
9.1.1.1. 
Revised Hammersmith Scale ......................................................................................50 
9.1.1.2. 
10-Meter Walk/Run ....................................................................................................50 
9.1.1.3. 
Timed Rise from Floor ...............................................................................................50 
9.1.1.4. 
6-Minute Walk Test ....................................................................................................50 
9.1.1.5. 
30-Second Sit-to-Stand ...............................................................................................51 
9.1.1.6. 
Hammersmith Functional Motor Scale Expanded ......................................................51 
9.1.1.7. 
Revised Upper Limb Module .....................................................................................51 
9.1.1.8. 
WHO Motor Development Milestones .......................................................................51 
9.1.1.9. 
Endurance Shuttle Nine Hole Peg Test ......................................................................51 
9.1.1.10. 
Endurance Shuttle Box and Block Test ......................................................................52 
9.1.1.11. 
Pediatric Evaluation of Disability Inventory Computer Adaptive Test ......................52 
9.1.1.12. 
Patient-reported Outcomes Measurement Information System ..................................52 
9.2. 
Pharmacokinetics Blood Sample Collection ..............................................................52 
9.3. 
Pharmacodynamics Blood Sample Collection............................................................53 
9.4. 
Immunogenicity Blood Sample Collection ................................................................53 
9.5. 
Biomarkers (Extension Period C Only) ......................................................................53 
10. 
ASSESSMENT OF SAFETY .....................................................................................54 
10.1. 
Safety Parameters .......................................................................................................54 

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10.1.1. 
Demographic/Medical History ...................................................................................54 
10.1.2. 
Vital Signs ..................................................................................................................54 
10.1.3. 
Weight and Height ......................................................................................................54 
10.1.4. 
Physical Examination .................................................................................................54 
10.1.5. 
Electrocardiogram .......................................................................................................54 
10.1.6. 
Concomitant Medications ...........................................................................................55 
10.1.7. 
Laboratory Assessments .............................................................................................55 
10.1.7.1. 
Hematology and Coagulation .....................................................................................55 
10.1.7.2. 
Blood Chemistry .........................................................................................................56 
10.1.7.3. 
Urinalysis ....................................................................................................................56 
10.1.7.4. 
Pregnancy Testing ......................................................................................................56 
10.2. 
Adverse and Serious Adverse Events .........................................................................57 
10.2.1. 
Definition of Adverse Events .....................................................................................57 
10.2.1.1. 
Adverse Event .............................................................................................................57 
10.2.1.2. 
Serious Adverse Event ................................................................................................57 
10.2.1.3. 
Dosing Errors ..............................................................................................................58 
10.2.1.4. 
Pregnancy ...................................................................................................................58 
10.2.1.5. 
Treatment-Emergent Adverse Event ..........................................................................58 
10.3. 
Adverse Event Monitoring .........................................................................................59 
10.3.1. 
Relationship to Study Drug (Causality Assessment) ..................................................59 
10.4. 
Assessment of Expectedness ......................................................................................60 
10.5. 
Common Terminology Criteria for Adverse Events ..................................................60 
10.6. 
Recording Adverse Events .........................................................................................60 
10.6.1. 
Instructions for Recording AEs in eCRF ....................................................................60 
10.6.1.1. 
Recording Diagnosis Versus Signs and Symptoms ....................................................60 
10.6.1.2. 
Abnormal Laboratory Values or Vital Signs ..............................................................61 
10.7. 
Reporting Serious Adverse Events .............................................................................61 
10.7.1. 
Serious Adverse Event Reporting ...............................................................................61 
10.7.1.1. 
Initial Reports .............................................................................................................61 
10.7.1.2. 
Follow-up Reports ......................................................................................................62 
10.7.1.3. 
Reporting Pregnancies ................................................................................................62 
10.7.1.4. 
Reporting to Institutional Review Board/Independent Ethics Committee by 
Investigator .................................................................................................................62 

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10.7.1.5. 
Unblinding a Patient’s Treatment During the Study ..................................................63 
10.7.2. 
Expedited Reporting by the Sponsor to a Regulatory Health Authority ....................63 
11. 
STATISTICS ..............................................................................................................64 
11.1. 
General Methodology .................................................................................................64 
11.2. 
Analysis Strategy ........................................................................................................64 
11.2.1. 
Safety Analyses ..........................................................................................................64 
11.2.2. 
Efficacy Analyses .......................................................................................................64 
11.2.3. 
Pharmacokinetic and Pharmacodynamic Analysis .....................................................65 
11.2.4. 
Anti-SRK-015 Antibody Analysis ..............................................................................65 
11.3. 
Sample Size Rationale ................................................................................................65 
11.4. 
Interim Analyses .........................................................................................................66 
11.4.1. 
Pharmacokinetic and Pharmacodynamic Interim Analysis ........................................66 
11.4.2. 
Safety and Efficacy Interim Analyses ........................................................................66 
12. 
STUDY ADMINISTRATION ...................................................................................68 
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................69 
13.1. 
Study Monitoring ........................................................................................................69 
13.2. 
Audits and Inspections ................................................................................................69 
13.3. 
Institutional Review Board/Independent Ethics Committee ......................................69 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................70 
15. 
ETHICS ......................................................................................................................71 
15.1. 
Ethics Review .............................................................................................................71 
15.2. 
Ethical Conduct of the Study ......................................................................................71 
15.3. 
Written Informed Consent and Assent .......................................................................71 
15.4. 
Patient Confidentiality ................................................................................................71 
16. 
DATA PROTECTION ...............................................................................................72 
16.1. 
Organizational and Technical Arrangements to Avoid Unauthorized Access, 
Disclosure, Dissemination, Alteration, or Loss of Information and Personal 
Data Processed ............................................................................................................72 
17. 
DATA HANDLING AND RECORDKEEPING .......................................................73 
17.1. 
Inspection of Records .................................................................................................73 
17.2. 
Retention of Records ..................................................................................................73 
18. 
PUBLICATION POLICY ..........................................................................................74 
19. 
LIST OF REFERENCES ............................................................................................75 

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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................18 
Table 2: 
Study Schedule of Assessments: Treatment Period....................................................32 
Table 3: 
Study Schedule of Assessments: Extension Period A (Extension A Visits 1-
15) ...............................................................................................................................34 
Table 4: 
Study Schedule of Assessments: Extension Period B (Extension B Visits 1-
15) ...............................................................................................................................36 
Table 5: 
Study Schedule of Assessments: Extension Period C (Extension C Visits 1-
15) ...............................................................................................................................38 
Table 6: 
Motor Function Outcome Measures ...........................................................................40 
Table 7: 
Efficacy Endpoints by Cohort ....................................................................................49 
Table 8: 
Paired T-test: Reject Null Hypothesis No Mean Change from Baseline ....................66 
Table 9: 
Unpaired T-test: Reject Null Hypothesis: No Mean Difference from Baseline .........66 
Table 10: Study Administrative Structure ..................................................................................68 
 
LIST OF FIGURES 
Figure 1: 
Study Schematic: Treatment Period ...........................................................................30 
Figure 2: 
Study Schematic: Extension Period A ........................................................................30 
Figure 3: 
Study Schematic: Extension Period B ........................................................................31 
Figure 4: 
Study Schematic: Extension Period C ........................................................................31 

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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
6MWT 
6-Minute Walk Test 
ADA 
antidrug antibody 
AE 
adverse event 
APTT 
activated partial thromboplastin time 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EIU 
exposure in utero 
EOS 
end-of-study 
ESBBT 
Endurance Shuttle Box and Block Test 
ESNHPT 
Endurance Shuttle Nine Hole Peg Test 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HFMSE 
Hammersmith Functional Motor Scale Expanded 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intention-to-Treat 
IV 
intravenous 
IWRS 
Interactive Web-based Randomization System 
mAb 
monoclonal antibody 
MAD 
multiple ascending dose 
NOAEL 
no-observed-adverse-effect level 

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Abbreviation or Specialist Term 
Explanation 
PD 
pharmacodynamic(s) 
PEDI-CAT 
Pediatric Evaluation of Disability Inventory Computer 
Adaptive Test 
PK 
pharmacokinetic(s) 
PT/INR 
prothrombin time/international normalized ratio 
PROMIS 
Patient-reported Outcomes Measurement Information System 
QOL 
quality of life 
RHS 
Revised Hammersmith Scale 
RULM 
Revised Upper Limb Module 
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SMA 
spinal muscular atrophy 
SMN 
survival motor neuron 
SMN upregulator 
SMN corrector 
SOP 
standard operating procedure 
SRK-015 
investigational, fully human, mAb that specifically binds to 
proforms of myostatin, which include proMyostatin and latent 
myostatin, thereby inhibiting myostatin activation 
SST 
Safety Surveillance Team 
TEAE 
treatment-emergent adverse event 
Tlim 
time to limitation 
UNS 
unscheduled 
US 
United States 
WHO 
World Health Organization 

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4. 
INTRODUCTION 
4.1. 
SRK-015 
Apitegromab (SRK-015) is an investigational, fully human, monoclonal antibody (mAb) that 
specifically binds to proforms of myostatin, which include proMyostatin and latent myostatin, 
thereby inhibiting myostatin activation. The antibody is produced in Chinese Hamster Ovary 
cells stably transfected with expression vectors encoding for the heavy and light chains of the 
antibody. SRK-015 is being developed for the treatment of spinal muscular atrophy (SMA) in 
pediatric and adult patients. SRK-015 is administered by intravenous (IV) infusion. 
4.2. 
Spinal Muscular Atrophy 
SMA is a rare, autosomal recessive neuromuscular disease characterized by degeneration of the 
motor neurons in the anterior horn of the spinal cord, resulting in atrophy of the voluntary 
muscles of the limbs and trunk. SMA directly results from reduced levels of survival motor 
neuron (SMN) protein, caused by homozygous deletions and, infrequently, mutations within the 
survival motor neuron 1 (SMN1) gene on chromosome 5q13.2. The lack of SMN protein causes 
the motor neurons to become dysfunctional and, eventually, to die. 
Despite being a rare disorder, SMA is the most common genetic cause of infant mortality and a 
major cause of childhood morbidity (Pearn 1973; Sugarman 2012). The reported birth prevalence 
of SMA ranges from 8.5 to 10.3 per 100,000 live births (Arkblad 2009; Jedrzejowska 2013; 
Prior 2010; Sugarman 2012). The clinical phenotype of patients with SMA can vary significantly 
between patients who die soon after birth to patients who live into adulthood without symptoms. 
A major determinant of clinical phenotype is the number of copies present of a second gene, 
SMN2. There is a normal variance of SMN2 gene copies in the general population where healthy 
individuals typically have 1 or 2 copies, and patients with SMA typically have 2 or 3 copies 
(Crawford 2012; Fang 2015). 
Prior to the development of advanced molecular medicine techniques that allow genotyping of 
both SMN1 and SMN2 copy numbers, SMA was diagnosed based on clinical presentation and 
categorized phenotypically based on the maximal motor milestone achieved and the age at 
symptom onset. This phenotypic classification system requires subjects to be followed for 
enough time to determine whether a milestone will or will not be achieved. Because subjects 
may have been enrolled into a clinical trial before they were old enough to achieve certain motor 
milestones, for example sitting independently, a classification system based on age of symptom 
onset was used for clinical trial enrollment (Finkel 2015). 
Type 0 or prenatal SMA is a rare type in which infants are born with clinical manifestations of 
disease, including major joint contractures and respiratory compromise, which result in a 
requirement for mechanical ventilation and ultimately lead to death at or shortly after birth 
(Dubowitz 1999; Finkel 2015; MacLeod 1999; Mercuri 2012). These patients usually have 
1 copy of the SMN2 gene. 
Type 1 SMA is the most common form of SMA and represents approximately 58% of the birth 
prevalence (Ogino 2004). More than 90% of patients with 2 copies of SMN2 will develop Type 1 
SMA (Feldkötter 2002), and these infants usually present with hypotonia, loss of motor function, 
and failure to achieve new milestones within the first 6 months of life. These infants are never 

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able to sit without support (De Sanctis 2016; Russman 2007; Wang 2007). The major cause of 
morbidity and mortality in patients with Type 1 SMA is pulmonary disease due to neuromuscular 
weakness (Wang 2007). In the absence of respiratory support, only 1.3% of infants with Type 1 
SMA survive beyond 24 months of age (Gregoretti 2013). 
Type 2 SMA represents approximately 29% of the birth prevalence (Ogino 2004). Patients with 
Type 2 SMA usually have 3 copies of the SMN2 gene but can vary between 2 and 4 copies. More 
than 80% of patients with 3 copies of SMN2 will develop Type 2 SMA (Feldkötter 2002). 
Children fail to achieve motor milestones because of proximal weakness and hypotonia that 
typically develop within the first 18 months of life. This group is generally defined by an ability 
to sit independently but inability to walk unaided (Rudnik-Schöneborn 2001). However, the 
progressive nature of the disease means some of these patients will lose their ability to sit 
independently over time (Faravelli 2015; Russman 2007; Wang 2007). Orthopedic and 
respiratory complications are a major cause of morbidity and mortality, and only 70% of patients 
with Type 2 SMA are alive at 25 years of age (Faravelli 2015). 
Type 3 SMA represents approximately 13% of the birth prevalence (Ogino 2004). Patients with 
Type 3 SMA usually have 3 or 4 copies of the SMN2 gene. More than 80% of patients with 
4 copies of SMN2 will develop Type 3 SMA (Feldkötter 2002). Milestone achievement can vary 
greatly in SMA Type 3; some patients may maintain their ability to walk, while other patients 
have a level of functioning that more closely resembles SMA Type 2 (Finkel 2015). The 
distinguishing milestone for SMA Type 3 is the ability to walk unaided; however, the majority of 
patients lose that function over time (Rudnik-Schöneborn 2001). Ambulatory patients with 
Type 3 SMA commonly suffer from substantial motor functional impairment, as evidenced by 
abnormal Hammersmith Functional Motor Scale Expanded (HFMSE) scores and 6-Minute Walk 
Test (6MWT) distances (Mercuri 2016; Montes 2010). Some patients with Type 3 have 
orthopedic problems that are comparable to those experienced by patients with SMA Type 2, 
although generally with later onset and decreased severity (Haaker 2013). 
Type 4 SMA is the mildest form of SMA, and its occurrence is rare (<1%). Patients with 
Type 4 SMA usually have 4 or more copies of the SMN2 gene. After symptom onset, which has 
been reported after 10 years of age but more commonly after 20 to 30 years of age (Wang 2007), 
patients experience mild to moderate muscle weakness and increasing disabilities. Patients are 
ambulatory, and their life expectancy is normal (Faravelli 2015). 
4.3. 
Current Therapies and Unmet Medical Need 
In some countries, SPINRAZA® (nusinersen) is approved for the treatment of pediatric and adult 
patients with SMA, EVRYSDI™ (risdiplam) is approved for the treatment of pediatric and adult 
patients ≥2 months of age with SMA, and ZOLGENSMA® (onasemnogene abeparvovec-xioi) is 
approved for the treatment of pediatric patients less than 2 years of age with SMA with bi-allelic 
mutations in the SMN1 gene. Nusinersen is an SMN2-directed antisense oligonucleotide and 
risdiplam is an SMN2-directed ribonucleic acid splicing modifier that are designed to treat SMA 
caused by mutations that lead to SMN protein deficiency. Onasemnogene abeparvovec-xioi is a 
recombinant adeno-associated virus vector 9-based gene therapy designed to deliver a copy of 
the gene encoding the human SMN protein. There are currently no approved muscle-directed 
therapies for the treatment of SMA. Additional medical care is supportive and focuses on 
respiratory support, nutritional support, and management of resulting musculotendinous 

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contractures and neuromuscular scoliosis through bracing, physical therapy, and surgery (Wang 
2007). 
SMN upregulator therapies (also referred to as SMN corrector therapies), such as nusinersen, 
onasemnogene abeparvovec-xioi, and other products in development (e.g., small molecule SMN 
upregulators) act primarily upon motor neurons to prevent further loss. While approved 
treatments have shown improvement in motor function in younger patients with SMA, they do 
not act directly on the muscle to primarily address already-existing atrophy and motor functional 
impairment in patients with symptomatic SMA. Consequently, there remains an unmet need for 
an effective muscle-directed therapy that can address muscle atrophy and motor functional 
impairment in patients with SMA. 
4.4. 
Safety Rationale for SRK-015 
SRK-015 has been evaluated in a single Phase 1 study (SRK-015-001). This two-part, 
randomized, double-blind, placebo-controlled, first-in-human trial was designed to evaluate the 
safety and tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of 
intravenously administered SRK-015 in adult healthy subjects. A total of 66 subjects were 
enrolled, including 40 subjects in Part A, single ascending dose (SAD) and 26 subjects in Part B, 
multiple ascending dose (MAD). Subjects in the SAD were randomized 3:1 to receive single 
doses of SRK-015 or placebo across 5 dosing cohorts (1, 3, 10, 20, and 30 mg/kg), while subjects 
in the MAD were randomized 3:1 to receive multiple biweekly doses (on Days 0, 14, and 28) of 
SRK-015 or placebo across 3 dosing cohorts (10, 20, and 30 mg/kg). Both parts of the study have 
been completed. 
Results of the study show that there were no dose-limiting toxicities (up to the highest dose 
tested of 30 mg/kg), deaths, subject discontinuations due to an adverse event (AE) related to 
SRK-015, serious adverse event (SAE) related to SRK-015, severe or life-threatening AEs 
related to SRK-015, or hypersensitivity reactions. The most common AE was headache in the 
SAD and postural dizziness in the MAD, which were observed in both the SRK-015 and placebo 
groups. Immunogenicity was assessed by antidrug antibody (ADA) testing, and all SRK-015 
treated subjects tested negative. 
Based upon PK analysis, SRK-015 displayed a well-behaved PK profile (e.g., low coefficient of 
variation) generally consistent with that observed with monoclonal antibodies. Drug exposure 
was dose proportional, and the serum half-life was 23 to 33 days across the SRK-015 dose 
groups in the SAD study. The findings support the investigation of a once every 4-week dosing 
regimen in this Phase 2 study (SRK-015-002). 
No toxicologically significant findings have been observed to date for SRK-015 across the good 
laboratory practice (GLP) nonclinical toxicology studies. The no-observed-adverse-effect level 
(NOAEL) was the highest dose tested of 300 mg/kg weekly in the 26-week adult rat study and 
7-week juvenile rat study. In addition, the NOAEL was the highest dose tested of 100 mg/kg 
weekly in the 4-week GLP nonclinical toxicology study in nonhuman primates and the 4-week 
GLP nonclinical toxicology study in rats. Based upon PK data from the SAD portion of the 
Phase 1 study, the drug exposure in this Phase 2 clinical study of monthly IV administrations of 
SRK-015 at the planned high-dose level of 20 mg/kg (or the maximum potential dose level of 
30 mg/kg) is predicted to be substantially less than that attained and evaluated in the nonclinical 
toxicity studies. 

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For further detail on the Phase 1 clinical results and nonclinical findings, including findings that 
were not toxicologically significant, please refer to the SRK-015 Investigator’s Brochure. 
4.5. 
Therapeutic Rationale for SRK-015 
Although progress has been made in the development of therapies addressing the SMN 
deficiencies, there remains an unmet medical need for a muscle-directed therapy that addresses 
the motor function deficits in SMA. By targeting the myostatin pathway (through the inhibition 
of myostatin activation), it is hypothesized that SRK-015 may address muscle atrophy and 
improve motor function (Han 2013). 
The preclinical data, mechanistic rationale, and translational insights of SRK-015 pharmacology 
and muscle biology highlight the relevance of the myostatin pathway as a therapeutic target in 
SMA. Based upon preclinical evidence, the muscle mass and function-building effects of 
myostatin inhibition disproportionately impact fast-twitch fibers; in SMA, there is prominent 
atrophy of fast-twitch fibers and associated functional impairment. SRK-015 (or its murine 
version) has demonstrated the ability to substantially increase fast-twitch fiber mass across 
multiple animal species, including nonhuman primates. In an SMA mouse model, treatment 
robustly increased muscle strength (as measured by torque) (Long 2018). 
Data from the Phase 1 clinical study (SRK-015-001) offer initial evidence that SRK-015 may 
have the pharmacologic profile necessary to suppress the myostatin pathway in humans. The PD 
of SRK-015 were evaluated through an assay measuring latent myostatin biomarker 
concentrations in the serum. These data demonstrated that SRK-015 treatment was able to 
successfully engage target, attain a plateau for this effect (thus, suggesting target saturation) even 
after a single treatment at doses of 3 mg/kg or greater, and sustain this effect for at least several 
months following a single dose of 20 mg/kg or greater. Relatively faster clearance of latent 
myostatin was observed with lower doses of SRK-015, suggesting that higher doses offer 
sustained target engagement. Together, these data provide evidence that systemic administration 
of SRK-015 at pharmacologically tractable doses in humans may successfully engage its target 
in the skeletal muscle, saturate this engagement, and sustain this saturation in a durable fashion. 
4.6. 
Study Rationale 
There remains an unmet need for an effective muscle-directed therapy that can address muscle 
atrophy and thereby improve motor function in patients with SMA despite advances in the 
development of SMN upregulator therapies. Through its novel mechanism, SRK-015 has the 
potential to produce a clinically meaningful effect on motor function in a broad population of 
patients with SMA who may or may not be on background SMN upregulator therapies 
(e.g., nusinersen). As such, SRK-015 has the potential to treat a severe disease and fulfill a 
significant unmet medical need for patients with SMA. Accordingly, this first study of SRK-015 
in patients with Type 2 and Type 3 SMA is designed to evaluate the safety and efficacy of 
SRK-015 in patients who are receiving background SMN upregulator therapy (Cohorts 1, 2, and 
3) and in those who are not (Cohort 1). The study will assess the effects of SRK-015 upon motor 
function outcome measures (e.g., HFMSE, Revised Hammersmith Scale [RHS], and Revised 
Upper Limb Module [RULM]) that are designed for SMA, validated in SMA, and considered 
clinically meaningful. In addition, the study will characterize the effect of SRK-015 upon other 
outcome measures relevant for neuromuscular disorders such as SMA. The sample sizes were 

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selected to enable meaningful assessments of the clinical effects of SRK-015 as compared to the 
otherwise anticipated course of disease based upon natural history as well as to characterize the 
safety of SRK-015. 
The treatment duration necessary to attain clinical effect in patients with SMA is unknown. The 
increases in muscle mass and strength seen in nonclinical studies can be apparent as early as after 
approximately a month of dosing. Longer treatment durations may be required in patients with 
SMA, particularly if the goal is to attain improvements in clinically meaningful motor function 
outcome measures. Accordingly, a period of 52 weeks has been selected to provide a reasonable 
period of time to observe a clinical effect upon motor function from inhibiting the activation of 
myostatin. Interim analyses will explore whether clinical effects are evident earlier. 
Three optional Extension Periods (52 weeks each) have been added to the study to observe the 
long-term safety and efficacy effects of SRK-015 and to demonstrate any potential treatment 
benefits for patients. 
Available data and mechanistic understanding support the investigation of SRK-015 in pediatric 
patients. Children represent a significant proportion of the SMA population with substantial 
unmet medical need and have the potential to benefit from a novel therapeutic approach 
addressing their muscle atrophy and motor functional impairment. There is no apparent biologic 
basis for suspecting that pediatric patients may have any uniquely elevated safety risk from 
blockade of the myostatin pathway. In addition, toxicologically significant findings were not 
observed in the 7-week juvenile rodent study, including at the highest dose tested (300 mg/kg IV 
SRK-015 weekly). Data from the SAD portion of the Phase 1 study demonstrated a generally 
well-behaved PK profile for SRK-015, and SRK-015 dosing will be weight-based in this Phase 2 
study. To initially confirm that drug exposure or target engagement in pediatric patients does not 
substantially differ from that observed in the Phase 1 study in adult healthy volunteers, interim 
PK and PD analyses will be conducted in a small number of patients in this Phase 2 study. Based 
upon these results, and taking into consideration any available safety data, the dose levels may be 
adjusted in this Phase 2 study. Any adjustment in dose level will not change the frequency of 
dosing (i.e., every 4 weeks) and the highest dose will not exceed 30 mg/kg, as tested in the 
Phase 1 study. 
4.7. 
Dose Rationale 
Based upon data from SRK-015-001, the first in-human study in healthy volunteers, multiple 
doses of up to 30 mg/kg were generally safe and well tolerated. PK results from the Phase 1 SAD 
study suggest that SRK-015 has a profile generally consistent with that observed of mAbs, 
including dose-proportionality and a low coefficient of variation. The serum half-life was 23 to 
33 days across the SRK-015 dose groups. The findings support the investigation of a once every 
4-week dosing regimen in this Phase 2 study. 
PD results suggest that SRK-015 treatment leads to robust increases in latent myostatin 
concentrations in the serum above baseline and demonstrate successful target engagement in 
humans. Moreover, the levels of target engagement attain a plateau, suggesting that the target has 
been saturated even with a single treatment of SRK-015 at doses of 3 mg/kg or greater. This 
level of PD marker appears to be sustained for approximately 84 days following a single 
20 mg/kg dose, suggesting that the PD effect is durable. 

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The 20 mg/kg high-dose arm is aimed at attaining target saturation rapidly (e.g., within several 
weeks after the first dose) and sustaining that saturation with chronic administration. Based upon 
PK data from the Phase 1 SAD study, the drug exposure from monthly IV administrations of 
SRK-015 at 20 mg/kg is predicted to be substantially less than that attained in the nonclinical 
toxicity studies to date. For further detail on the Phase 1 PK and PD results, please refer to the 
SRK-015 Investigator’s Brochure. 
Dose exploration will be conducted in this study by including a low-dose arm of 2 mg/kg. At this 
dose level, it is anticipated that target saturation will not be attained upon the first dose and thus 
would require additional dosing. By characterizing the time course of clinical effect from this 
low-dose arm and comparing it with that observed from the 20 mg/kg level, the relationship 
between drug exposure and therapeutic effect over time can be interrogated. Insights into the 
level of drug exposure necessary to initiate improvements in motor function will also be attained. 
Together, results from this analysis will inform the dosing regimen for future clinical studies of 
SRK-015 in SMA. 
The results of the prespecified 6-month safety and efficacy interim analyses in this study, 
including greater improvements in HFMSE scores for the high-dose arm and no identification of 
safety signals, supported a change in dose for Cohort 3 patients from low-dose (2 mg/kg) to 
high-dose (20 mg/kg) SRK-015 during Extension Period A (See Section 6.2). The preliminary 
results of the 12-month analysis continue to support the dose change. For further details on the 
Phase 2 safety and efficacy analyses results please refer to the SRK-015 Investigator’s Brochure. 

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5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1. 
Primary Objectives for Both the Treatment Period and Extension 
Periods 
The primary objectives of this study are: 
• To assess safety and tolerability of SRK-015 in patients with later-onset (e.g., Type 2 
and Type 3) SMA 
• To assess the efficacy of SRK-015 by assessing changes in motor function outcome 
measures in 3 separate predefined cohorts 
5.2. 
Secondary Objectives for Both the Treatment Period and Extension 
Periods 
The secondary objectives defined for this study are: 
• To characterize the PK of SRK-015 
• To evaluate the PD effects of SRK-015 
• To evaluate time to therapeutic effect between low- and high-dose SRK-015 in a 
predefined cohort (Cohort 3) 
• To evaluate the immunogenicity of SRK-015 
• To evaluate the effect of SRK-015 on quality of life 

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6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
Study SRK-015-002 is an active treatment study of SRK-015 in patients age 2 through 21 years 
old with later-onset SMA. Patients may receive SRK-015 as monotherapy or in addition to an 
SMN upregulator therapy approved for SMA. 
The study will be conducted at approximately 20 study sites across the US and Europe and will 
enroll approximately 55 patients with SMA across 3 separate parallel subpopulations 
subsequently described as cohorts: 
• Cohort 1, N=20: Ambulatory Type 3 patients, age 5 through 21 years old, at least 
10 of whom are not receiving an approved SMA treatment, as well as patients already 
receiving an approved SMA treatment that had been started after the patient turned 
5 years old. 
• Cohort 2, N=15: Type 2 or nonambulatory Type 3 patients, age 5 through 21 years 
old, already receiving an approved SMA treatment that had been started after the 
patient turned 5 years old. 
• Cohort 3, N=20: Type 2 patients, age ≥2 years old, already receiving an approved 
SMA treatment that had been started before the patient turned 5 years old. 
Patient participation in the study will consist of 3 parts: Screening, Treatment, and Follow-up. 
1. During the Screening Period, all patient screening and eligibility determinations will be 
conducted after informed consent (and, as required by local authorities, patient informed 
assent) has been provided and within 28 days prior to first dose. Screening motor 
function outcome measures will be conducted at least 7 days prior to the first dose. All 
subsequent motor function outcome measures will be conducted within 96 hours prior to 
dosing. 
2. During the 52-week Treatment Period, patients enrolled in Cohorts 1 and 2 will receive 
high-dose (20 mg/kg) SRK-015 and patients enrolled in Cohort 3 will be randomized 
(1:1) in a blinded manner to receive either low-dose (2 mg/kg) or high-dose (20 mg/kg) 
SRK-015 (Figure 1). All treatments will be administered by IV infusion over 
approximately 2 hours once every 4 weeks. The first dose will be administered on Day 0 
and the final dose on Day 336, for a total of 13 doses. There will be a ±7-day window 
around each dosing visit, with a minimum of 21 days and a maximum of 35 days between 
doses. 
During the Treatment Period, patients will be monitored at the study site through 
approximately 2 hours postdose. If there are no acute reactions following the first 2 doses 
for a patient, and if the Investigator determines that it would be safe to do so, the infusion 
duration can be changed to less than 2 hours but no shorter than 1 hour. 
Following each dose, patients will be contacted by the site within 7 days as a safety 
check-in (in the Treatment Period only). Patients will be seen in clinic 14 days after the 
first dose. After the second dose, visits will occur every 4 weeks through the end of the 

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study (Table 2). All dosing and motor function outcome measures will be conducted at 
the study site during the Treatment Period. 
The last Treatment Period visit will be on Day 364 (V15). 
Total study participation for an individual patient who completes the Treatment Period 
will consist of approximately 4 weeks for Screening, 52 weeks of study visits, and, if the 
patient does not enroll into Extension Period A, 12 weeks of Safety Follow-up for a total 
duration of approximately 68 weeks (approximately 16 months). 
Patients who complete the 52-week Treatment Period will have the option to enroll into 
Extension Period A for an additional 52-week period (Figure 2). There will be no 
interruption in dosing between the completion of the Treatment Period and the start of 
Extension Period A. The first dose in Extension Period A will be administered on 
Day 364 (E1), following completion of the Treatment Period at V15, and the final dose 
will be administered on Day 700 (E13), for a total of 13 doses. 
Total study participation for an individual patient who completes both the Treatment 
Period and Extension Period A will consist of approximately 4 weeks for Screening, 104 
weeks of study visits, and 12 weeks of Safety Follow-up for a total duration of 
approximately 120 weeks (approximately 28 months). 
Patients who complete Extension Period A will have the option to enroll into Extension 
Period B for an additional 52-week period (Figure 3). There will be no interruption in 
dosing between the completion of Extension Period A and the start of Extension Period 
B. The first dose in Extension Period B will be administered on Day 728 (EB1), 
following completion of Extension Period A on Day 728 (E14), and the final dose will be 
administered on Day 1064 (EB13), for a total of 13 doses. 
Total study participation for an individual patient who completes the Treatment Period 
and Extension Periods A and B will consist of approximately 4 weeks for Screening, 156 
weeks of study visits, and 12 weeks of Safety Follow-up for a total duration of 
approximately 172 weeks (approximately 40 months). 
Patients who complete Extension Period B will have the option to enroll into Extension 
Period C for an additional 52-week period (Figure 4). There will be no interruption in 
dosing between the completion of Extension Period B and the start of Extension 
Period C. The first dose in Extension Period C will be administered on Day 1092 (EC1), 
following completion of Extension Period B on Day 1092 (EB14), and the final dose will 
be administered on Day 1428 (EC13), for a total of 13 doses. 
Total study participation for an individual patient who completes the Treatment Period 
and Extension Periods A, B, and C will consist of approximately 4 weeks for Screening, 
208 weeks of study visits, and 12 weeks of Safety Follow-up for a total duration of 
approximately 224 weeks (approximately 52 months). 
All treatments will be administered by IV infusion over 1 to 2 hours once every 4 weeks. 
There will be a ±7-day window around each dosing visit, with a minimum of 21 days and 
a maximum of 35 days between doses. 
During the Extension Periods, patients will be monitored at the study site through 
approximately 1 hour postdose. 

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3. Patients who complete the 52-week Treatment Period and choose not to enroll in optional 
Extension Period A will be followed for a 12-week Safety Follow-up Period after Day 
364 (V15). These patients will have a total of 13 doses. Patients who complete the 52-
week Extension Period A and choose not to enroll in optional Extension Period B will be 
followed for a 12-week Safety Follow-up Period after Day 728 (E14). These patients will 
have a total of 26 doses. Patients who complete the 52-week Extension Period B and 
choose not to enroll in optional Extension Period C will be followed for a 12-week Safety 
Follow-up Period after Day 1092 (EB14). These patients will have a total of 39 doses. 
Patients who complete the 52-week Extension Period C may be offered the option to 
enter a separate long-term safety extension trial at that time. Patients who complete the 
52-week Extension Period C and choose not to enroll in the separate long-term safety 
extension trial will be followed for a 12-week Safety Follow-up Period after Day 1456 
(EC14). These patients will have a total of 52 doses. 
6.2. 
Treatment Assignment 
Eligible patients in Cohorts 1 and 2 will receive high-dose (20 mg/kg) SRK-015. Patients in 
Cohort 3 will be randomized 1:1 to low- (2 mg/kg) or high-dose (20 mg/kg) SRK-015 without 
stratification for the duration of the Treatment Period. Based on the results of the prespecified 
6-month safety and efficacy interim analyses (data cutoff date of 20 August 2020), any Cohort 3 
patients who were randomized to receive low-dose (2 mg/kg) SRK-015 will be re-assigned to 
receive high-dose (20 mg/kg) SRK-015 after completion of the Treatment Period. The 
preliminary results of the 12-month analysis (database lock date of 19 January 2021) continue to 
support the dose change. For further detail on the Phase 2 safety and efficacy analyses results 
please refer to the SRK-015 Investigator’s Brochure. Due to the variability in timing of 
regulatory authority and/or Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approvals, the timepoint at which patients who received the low dose (2 mg/ kg) will begin 
receiving the high dose (20 mg/kg) during Extension Period A will vary. 

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Figure 1: 
Study Schematic: Treatment Period 
 
Figure 2: 
Study Schematic: Extension Period A 
 
 

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Figure 3: 
Study Schematic: Extension Period B 
 
 
Figure 4: 
Study Schematic: Extension Period C 
 
 

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Table 2: 
Study Schedule of Assessments: Treatment Period 
Activity/Assessment 
Screening 
Treatment Period  
Follow-up  
Visit 
Time Point (Study Daya) 
-28 to -1 
V1 
0 
V2 
14 
V3 
28 
V4 
56  
V5 
84  
V6 
112  
V7 
140 
V8 
168 
V9 
196 
V10 
224 
V11 
252  
V12 
280  
V13 
308  
V14 
336  
V15 
364  
UNS 
V16 
392 
V17 
448/EOS/ 
ET 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics & Medical Historyc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Testd 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
Weighte 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Heightf 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
Physical Examinationg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Safety Labsi 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
12-lead ECGj 
X 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
PK and PD Samplingk 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Antidrug Antibody Samplingl 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Randomizationm 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Motor Function Outcome Measures 
b,f,,n  
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
QOLo 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
Site Check-inp 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Adverse Events 
To be collected from the date that the ICF is signed through the last study visit 
Concomitant Therapy 
To be collected from the date that the ICF is signed through the last study visit 
ECG = electrocardiogram; EOS = end-of-study; ET = early termination; ICF = informed consent form; IV = intravenous; PD = pharmacodynamic; PEDI-CAT: 
Pediatric Evaluation of Disability Inventory Computer Adaptive Test; PK = pharmacokinetic; PROMIS = Patient-reported Outcomes Measurement Information 
System; QOL = quality of life; UNS = unscheduled. 

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a Study visits after Day 0 have a ±7-day window, excluding Day 14, which has a ±1-day window. Visit assessments may be conducted over multiple days within 
the visit window, as needed and in compliance with protocol requirements for the timing of each assessment. 
b Screening motor function outcome measures must be completed at least 7 days prior to the first infusion on Day 0. All subsequent motor function outcome 
measures will be conducted within 96 hours prior to dosing. 
c Includes history of present illness. 
d Females of childbearing potential only. Urine or serum test is acceptable; however, positive urine tests must be confirmed with serum testing. Testing may be 
performed more frequently as per local requirements. The urine pregnancy test used is the Alere hCG cassette (25mIU/mL) and according to the product 
manufacturer, has >99% sensitivity. 
e Weight is collected within 48 hours of each dose to calculate weight-based dosing. 
f Height is collected at visits where the motor function outcome measures are conducted. Ulna length may be used to estimate height for patients who are 
nonambulatory or needs standing support. 
g Changes in pubertal development must be assessed if not deemed physically mature at Screening. If menarche occurs during the study, the child will be deemed 
of childbearing potential and immediate pregnancy status will be checked. Further study drug can only be given if pregnancy status is negative. Contraception 
and pregnancy monitoring will be performed as outlined in the protocol. 
h Heart rate, blood pressure, and respiratory rate are collected preinfusion, every 15 minutes (±5 minutes) during the infusion, at the end of the infusion, and 
1 and 2 hours (±15 minutes) postinfusion. Body temperature will be collected preinfusion on dosing days. 
i Clinical safety labs include serum chemistry, hematology, urinalysis, and coagulation. Labs are collected preinfusion at dosing visits. 
j 12-lead ECGs are collected after 5 minutes of rest, in triplicate and at least 1-2 minutes apart. ECGs are collected within 2 hours prior to the start of the 
infusion. Unscheduled ECGs may be performed as clinically necessary. 
k Blood samples for PK and PD are collected within 2 hours prior to the start of the infusion at dosing visits. An additional sample is collected via peripheral IV 
2 hours (±1 hour) after completion of the infusion on Day 0, Day 140 (PK only), and Day 336 (PK only). 
l Blood sample for anti-SRK-015 antibody testing is collected within 2 hours prior to the start of the infusion at dosing visits. 
m Patients in Cohort 3 will be randomized to low- or high-dose SRK-015 within 24 hours prior to the first infusion on Day 0. 
n See Table 6 for motor function outcome measures conducted for each cohort. Unscheduled motor function outcome measures may be performed as needed. 
o QOL collected using the PROMIS Fatigue Questionnaire and PEDI-CAT. If the PEDI-CAT and/or PROMIS are not available in the native language, they 
should not be completed. Unscheduled QOL questionnaires may be performed as needed. 
p Sites contact patients within 7 days following each infusion to collect information on adverse events and concomitant medications. 
 
 
 
 
 

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Table 3: 
Study Schedule of Assessments: Extension Period A (Extension A Visits 1-15) 
Activity/Assessment 
Extension Period A 
Follow-Up/ 
Other  
Visit 
Time Point (Study Daya) 
E1 364 c 
E2 
392 
E3 
420 
E4 
 448  
E5 
476  
E6 
504 
E7 
532 
E8 
560 
E9 
588 
E10 
616  
E11 
644 
E12 
672  
E13 
700  
E14 
728 
E -
UNS 
E15 
812/EOS/
ET 
Informed Consento 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Testd 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
Weighte 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Heightf 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
X 
X 
Physical Examinationg 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Vital Signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Safety Labsi 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
X 
12-lead ECGj 
X 
 
 
X 
 
 
X  
 
 
X  
 
 X  
 
X 
X 
PK and PD Samplingk 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
Antidrug Antibody 
Samplingl 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
Study Drug Administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Motor Function Outcome 
Measures b,f,m  
 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
X 
X 
QOLn 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
X 
X 
Adverse Events 
To be collected from the date that the ICF is signed through the last study visit 
Concomitant Therapy 
To be collected from the date that the ICF is signed through the last study visit 
ECG = electrocardiogram; EOS = end-of-study; ET = early termination; ICF = informed consent form; IV = intravenous; PD = pharmacodynamic; PEDI-CAT: 
Pediatric Evaluation of Disability Inventory Computer Adaptive Test; PK = pharmacokinetic; PROMIS = Patient-reported Outcomes Measurement Information 
System; QOL = quality of life; UNS = unscheduled. 
a Study visits have a ±7-day window. Visit assessments may be conducted over multiple days within the visit window, as needed and in compliance with 
protocol requirements for the timing of each assessment. 
For patients who enroll 
into Extension Period A, 
assessments will merge 
between Treatment 
Period Day 364 (V15) 
and Extension Period A 
Day 364 (E1). Study drug 
administration and 
PK/PD/ADA Sampling 
will only be performed 
for patients who enroll 
into Extension Period A. 

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b All motor function outcome measures will be conducted within 96 hours prior to dosing. 
c Treatment Period Day 364 (Visit 15) and Extension Period A Day 364 (E1) occur on the same day. Treatment Period V15 will serve as the last Treatment 
Period visit and Extension Period A E1 will serve as the first visit for Extension Period A. There will not be any duplicate assessments performed. 
d Females of childbearing potential only. Urine or serum test is acceptable; however, positive urine tests must be confirmed with serum testing. Testing may be 
performed more frequently as per local requirements. The urine pregnancy test used is the Alere hCG cassette (25mIU/mL) and according to the product 
manufacturer, has >99% sensitivity. 
e Weight is collected within 48 hours of each dose to calculate weight-based dosing. 
f Height is collected at visits where the motor function outcome measures are conducted. Ulna length may be used to estimate height for patients who are 
nonambulatory or not able to stand independently. 
g Changes in pubertal development must be assessed if not deemed physically mature during Treatment Period. If menarche occurs during the study, the child 
will be deemed of childbearing potential and immediate pregnancy status will be checked. Further study drug can only be given if pregnancy status is negative. 
Contraception and pregnancy monitoring will be performed as outlined in the protocol. 
h Heart rate, blood pressure, and respiratory rate are collected preinfusion, every 15 minutes (±5 minutes) during the infusion, at the end of the infusion, and 
1 hour (±15 minutes) postinfusion. Body temperature will be collected preinfusion on dosing days. 
i Clinical safety labs include serum chemistry, hematology, urinalysis, and coagulation. Labs are collected preinfusion at dosing visits. 
j 12-lead ECGs are collected after 5 minutes of rest, in triplicate and at least 1-2 minutes apart. ECGs are collected within 2 hours prior to the start of the 
infusion. Unscheduled ECGs may be performed as clinically necessary. 
k Blood samples for PK and PD are collected within 2 hours prior to the start of the infusion at dosing visits. An additional sample is collected via peripheral IV 
1 hour (+ 30-minute window) after completion of the infusion on Day 700 (PK only). 
l Blood sample for anti-SRK-015 antibody testing is collected within 2 hours prior to the start of the infusion at dosing visits. 
m See Table 6 for motor function outcome measures conducted for each cohort. Unscheduled motor function outcome measures may be performed as needed. 
n QOL collected using the PROMIS Fatigue Questionnaire and PEDI-CAT. If the PEDI-CAT and/or PROMIS are not available in the native language, they 
should not be completed. Unscheduled QOL questionnaires may be performed as needed. 
o Patients may consent to participate in Extension Period A at any time prior to V15/E1 or at V15/E1. 
 
 
 
 
 
 
 
 
 

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Table 4: 
Study Schedule of Assessments: Extension Period B (Extension B Visits 1-15) 
Activity/Assessment 
Extension Period B 
Follow-Up/ 
Other  
Visit 
Time Point (Study 
Daya) 
EB1o 
728 
EB2 
756 
EB3 
784 
EB4 
 812  
EB5 
840  
EB6 
868 
EB7 
896 
EB8 
924 
EB9 
952 
EB10 
980  
EB11 
1008 
EB12 
1036  
EB13 
1064  
EB14 
1092 
EB -
UNS 
EB15 
1176 
/EOS/ET 
Informed Consentn 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Testc 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
Weightd 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Heighte 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
X 
X 
Physical Examinationf 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Vital Signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Safety Labsh 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
X 
12-lead ECGi 
X 
 
 
X 
 
 
X  
 
 
X  
 
 
 
X 
X 
PK and PD Samplingj 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
X 
Antidrug Antibody 
Samplingk 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
X 
Study Drug 
Administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Motor Function 
Outcome Measuresb,e,l  
 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
X 
X 
QOLm 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
X 
X 
Adverse Events 
To be collected from the date that the ICF is signed through the last study visit 
Concomitant Therapy 
To be collected from the date that the ICF is signed through the last study visit 
For patients who enroll 
into Extension Period 
B, assessments will 
merge between 
Extension Period A 
Day 728 (E14) and 
Extension Period B 
Day 728 (EB1). Study 
drug administration 
will only be performed 
for patients who enroll 
into Extension 
Period B. 

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ECG = electrocardiogram; EOS = end-of-study; ET = early termination; ICF = informed consent form; IV = intravenous; PD = pharmacodynamic; PEDI-CAT: 
Pediatric Evaluation of Disability Inventory Computer Adaptive Test; PK = pharmacokinetic; PROMIS = Patient-reported Outcomes Measurement Information 
System; QOL = quality of life; UNS = unscheduled. 
a Study visits have a ±7-day window. Visit assessments may be conducted over multiple days within the visit window, as needed and in compliance with 
protocol requirements for the timing of each assessment. 
b All motor function outcome measures will be conducted within 96 hours prior to dosing. 
c Females of childbearing potential only. Urine or serum test is acceptable; however, positive urine tests must be confirmed with serum testing. Testing may be 
performed more frequently as per local requirements. The urine pregnancy test used is the Alere hCG cassette (25mIU/mL) and according to the product 
manufacturer, has >99% sensitivity. 
d Weight is collected within 48 hours of each dose to calculate weight-based dosing. 
e Height is collected at visits where the motor function outcome measures are conducted. Ulna length may be used to estimate height for patients who are 
nonambulatory or not able to stand independently. 
f Changes in pubertal development must be assessed if not deemed physically mature during Extension Period A. If menarche occurs during the study, the child 
will be deemed of childbearing potential and immediate pregnancy status will be checked. Further study drug can only be given if pregnancy status is negative. 
Contraception and pregnancy monitoring will be performed as outlined in the protocol. 
g Heart rate, blood pressure, and respiratory rate are collected preinfusion, every 15 minutes (±5 minutes) during the infusion, at the end of the infusion, and 
1 hour (±15 minutes) postinfusion. Body temperature will be collected preinfusion on dosing days. 
h Clinical safety labs include serum chemistry, hematology, urinalysis, and coagulation. Labs are collected preinfusion at dosing visits. 
i 12-lead ECGs are collected after 5 minutes of rest, in triplicate and at least 1-2 minutes apart. ECGs are collected within 2 hours prior to the start of the 
infusion. Unscheduled ECGs may be performed as clinically necessary. 
j Blood samples for PK and PD are collected within 2 hours prior to the start of the infusion at dosing visits. An additional sample is collected via peripheral IV 
1 hour (+ 30-minute window) after completion of the infusion on Day 1008 (PK only). 
k Blood sample for anti-SRK-015 antibody testing is collected within 2 hours prior to the start of the infusion at dosing visits. 
l See Table 6 for motor function outcome measures conducted for each cohort. Unscheduled motor function outcome measures may be performed as needed. 
m QOL collected using the PROMIS Fatigue Questionnaire and PEDI-CAT. If the PEDI-CAT and/or PROMIS are not available in the native language, they 
should not be completed. Unscheduled QOL questionnaires may be performed as needed. 
n Patients may consent to participate in Extension Period B at any time prior to E14/EB1 or at E14/EB1. 
o Extension Period A Day 728 (E14) and Extension Period B Day 728 (EB1) occur on the same day. Extension Period A E14 will serve as the last Extension
Period A visit and Extension Period B EB1 will serve as the first visit for Extension Period B. There will not be any duplicate assessments performed.

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Table 5: 
Study Schedule of Assessments: Extension Period C (Extension C Visits 1-15) 
Activity/Assessment 
Extension Period C 
Follow-Up/Other 
Visit 
Time Point (Study 
Daya)
EC1o 
1092 
EC2 
1120 
EC3 
1148 
EC4 
1176  
EC5 
1204  
EC6 
1232 
EC7 
1260 
EC8 
1288 
EC9 
1316 
EC10 
1344  
EC11 
1372 
EC12 
1400  
EC13 
1428  
EC14 
1456 
EC -
UNS 
EC15 
1540 
/EOS/ET 
Informed Consentn 
X 
Pregnancy Testc 
X 
X 
X 
X 
X 
Weightd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Heighte 
X 
X 
X 
X 
X 
Physical Examinationf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Safety Labsh 
X 
X 
X 
X 
X 
X 
X 
12-lead ECGi
X 
X 
X 
X 
X 
PK and PD Samplingj 
X 
X 
X 
X
p 
X 
Antidrug Antibody 
Samplingk
X 
X 
X 
X
p 
X 
Study Drug 
Administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Motor Function 
Outcome Measuresb,e,l
X 
X 
X 
X 
X 
QOLm
X 
X 
X 
X 
X 
Adverse Events 
To be collected from the date that the ICF is signed through the last study visit 
Concomitant Therapy 
To be collected from the date that the ICF is signed through the last study visit 
For patients who enroll 
into Extension Period 
C, assessments will 
merge between 
Extension Period B 
Day 1092 (EB14) and 
Extension Period C 
Day 1092 (EC1). Study 
drug administration 
will only be performed 
for patients who enroll 
into Extension 
Period C. 

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ECG = electrocardiogram; EOS = end-of-study; ET = early termination; ICF = informed consent form; IV = intravenous; PD = pharmacodynamic; PEDI-CAT: 
Pediatric Evaluation of Disability Inventory Computer Adaptive Test; PK = pharmacokinetic; PROMIS = Patient-reported Outcomes Measurement Information 
System; QOL = quality of life; UNS = unscheduled. 
a Study visits have a ±7-day window. Visit assessments may be conducted over multiple days within the visit window, as needed and in compliance with 
protocol requirements for the timing of each assessment. 
b All motor function outcome measures will be conducted within 96 hours prior to dosing. 
c Females of childbearing potential only. Urine or serum test is acceptable; however, positive urine tests must be confirmed with serum testing. Testing may be 
performed more frequently as per local requirements. The urine pregnancy test used is the Alere hCG cassette (25mIU/mL) and according to the product 
manufacturer, has >99% sensitivity. 
d Weight is collected within 48 hours of each dose to calculate weight-based dosing. 
e Height is collected at visits where the motor function outcome measures are conducted. Ulna length may be used to estimate height for patients who are 
nonambulatory or not able to stand independently. 
f Changes in pubertal development must be assessed if not deemed physically mature during Extension Period B. If menarche occurs during the study, the child 
will be deemed of childbearing potential and immediate pregnancy status will be checked. Further study drug can only be given if pregnancy status is negative. 
Contraception and pregnancy monitoring will be performed as outlined in the protocol. 
g Heart rate, blood pressure, and respiratory rate are collected preinfusion, every 15 minutes (±5 minutes) during the infusion, at the end of the infusion, and 
1 hour (±15 minutes) postinfusion. Body temperature will be collected preinfusion on dosing days. 
h Clinical safety labs include serum chemistry, hematology, urinalysis, and coagulation. Labs are collected preinfusion at dosing visits. 
i 12-lead ECGs are collected after 5 minutes of rest, in triplicate and at least 1-2 minutes apart. ECGs are collected within 2 hours prior to the start of the infusion 
and within 1 hour after the end of infusion at Visit EC1 and EC13. Unscheduled ECGs may be performed as clinically necessary. 
j Blood samples for PK and PD are collected within 2 hours prior to the start of the infusion at dosing visits. An additional sample is collected via peripheral IV 
1 hour (+ 30-minute window) after completion of the infusion at Visit EC1 (Day 1092) and EC13 (Day 1428) (PK only). 
k Blood sample for anti-SRK-015 antibody testing is collected within 2 hours prior to the start of the infusion at dosing visits. 
l See Table 6 for motor function outcome measures conducted for each cohort. Unscheduled motor function outcome measures may be performed as needed. 
m QOL collected using the PROMIS Fatigue Questionnaire and PEDI-CAT. If the PEDI-CAT and/or PROMIS are not available in the native language, they 
should not be completed. Unscheduled QOL questionnaires may be performed as needed. 
n Patients may consent to participate in Extension Period C at any time prior to EB14/EC1 or at EB14/EC1. 
o Extension Period B Day 1092 (EB14) and Extension Period C Day 1092 (EC1) occur on the same day. Extension Period B EB14 will serve as the last Extension
Period B visit and Extension Period C EC1 will serve as the first visit for Extension Period C. There will not be any duplicate assessments performed.
p PK/PD/ADA samples will only be collected at unscheduled visits when SRK-015 is administered on the same day. Please refer to footnotes j and k for sample 
collection details. 

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Table 6: 
Motor Function Outcome Measures 
Cohort 1 
Cohorts 2 and 3 
• 
Revised Hammersmith Scale (RHS) 
• 
6-Minute Walk Test (6MWT) 
• 
30-Second Sit-to-Stand 
• 
10-Meter Walk/Run (from RHS) 
• 
Timed Rise from Floor (from RHS) 
 
• 
Hammersmith Functional Motor Scale 
Expanded (HFMSE) 
• 
World Health Organization (WHO) Motor 
Development Milestones 
• 
Revised Upper Limb Module (RULM) 
• 
Endurance Shuttle Nine Hole Peg Test 
(ESNHPT) or Endurance Shuttle Box and Block 
Test (ESBBT)a 
a Patients who score ≤3 on Item A of the RULM at Screening will perform the ESNHPT at Screening and all 
subsequent assessments, while patients who score >3 on Item A of the RULM at Screening will perform the ESBBT 
at Screening and all subsequent assessments. If patient maxes out of an endurance test, the PT Advisory Board will 
be consulted to potentially change assessment designation. b The motor function outcome measures will be 
videotaped for educational and training purposes to ensure that they are being conducted properly and consistently 
by the physical therapists, upon consent. 
6.3. 
Safety Oversight and Stopping Rules 
6.3.1. 
Safety Surveillance Team 
A safety surveillance team (SST) will review safety data throughout the duration of the study 
(inclusive of Treatment, Extension and Safety Follow-up Periods) to assess patient safety. The 
SST will review safety data approximately every 6 months, and on an ad hoc basis as needed. 
Prior to Protocol Version 5.0, the SST review was approximately every 12 weeks. Safety reviews 
prepared by the independent Clinical Research Organization will be provided to a core team 
comprised of the Scholar Rock Medical Director, the Scholar Rock Product Safety Lead, the 
Medical Monitor, an independent biostatistician, and a physician not participating as an 
Investigator in the study. To further assist in the safety assessments, the core SST may request 
that other individuals such as SMA experts or others within their organizations review the data 
and participate in the discussions. Data tables and listings will be provided to the SST by a 
biostatistician as will be described in the statistical analysis plan (SAP). The SST reviews will 
not include any efficacy data. The responsibilities and actions of the SST will be governed by a 
separate SST charter outside of this protocol. 
6.3.2. 
Pharmacokinetic Criteria for Dose Adjustment 
The SST will review PK and PD data for each cohort as part of a prespecified interim analysis 
(refer to Section 11.4). Drug exposure and target engagement levels in patients with SMA will be 
evaluated to compare them to the levels seen in the Phase 1 healthy adult study. Data from 
multiple cohorts may be combined as necessary and will be provided by a biostatistician. Based 
on these results, and taking into consideration any available safety data, cohort-specific dose 
levels may be adjusted. Any adjustment in dose level will not change the frequency of dosing 
(i.e., every 4 weeks) and the highest dose will not exceed 30 mg/kg, as tested in the Phase 1 
study. 

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6.3.3. 
Study Stopping Rules 
Dosing in the study may be suspended at any time for an emergent safety concern by the Medical 
Monitor in consultation with the other core SST members until the SST can completely evaluate 
the event(s) and recommend an appropriate course of action. 
The SST may make recommendations to restart dosing and continue the study with no changes, 
continue the study with changes to the protocol, terminate the study, or require more data, input, 
and deliberation prior to making a decision. Criteria for study termination are based on the 
assessment of safety concerns that may arise during the conduct of the study or from data from 
the SRK-015 preclinical and clinical program. The study may be discontinued at any time at the 
Sponsor’s discretion, or if the SST determines that further drug exposure would pose an undue 
risk to patients. 
If the study is terminated prematurely, all Investigators, regulatory authorities and IRBs/ IECs 
will be notified promptly. Patients will continue to be followed for 12 weeks after their final 
dose. 
6.3.4. 
Individual Stopping Rules 
Dosing for any individual patient may be suspended or discontinued if the patient experiences an 
SAE related to SRK-015 or a clinically significant non-serious AE related to SRK-015, that in 
the assessment of the Investigator and in consultation with the Medical Monitor, warrants 
suspension or discontinuation from further dosing for that patient’s well-being. For patients who 
have had their dosing suspended, dosing may resume only after their AE has resolved and only if 
it would be considered safe to do so in the assessment of the Investigator (and in consultation 
with the Medical Monitor). For patients who have discontinued dosing, the patient will continue 
to be followed for 12 weeks after their final dose or until the resolution of any ongoing clinically 
significant AE, whichever occurs later. (For the definition of AE resolution, please refer to 
Section 10.2.1.) 
Dosing of SRK-015 for an individual patient may also be suspended or discontinued for safety 
concerns other than those described above based on review by the SST or at the discretion of the 
Investigator if he/she feels the patient’s safety may be threatened. The Investigator may ask for 
an ad hoc SST meeting to be held for any single event or combination of events that in his/her 
professional opinion may jeopardize the safety of the patient or the reliability of the data. 
Patients who develop either an SAE or other toxicity meeting the individual stopping criteria will 
be carefully monitored, which may include the following at the discretion of the Investigator: 
• Additional clinical laboratory tests and/or other clinical investigations 
• Additional visits or extended duration of follow-up 
• Obtaining a specialist consultation 
 

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7. 
SELECTION AND WITHDRAWAL OF PATIENTS 
7.1. 
Patient Inclusion Criteria 
1. Age 5 through 21 years old at the time of Screening for Cohorts 1 and 2; Age ≥2 years 
old at the time of Screening for Cohort 3 
2. Estimated life expectancy >2 years from Screening 
3. Informed consent document signed by the patient if the patient is legally an adult. If the 
patient is legally a minor, informed consent document signed by the patient’s parent or 
legal guardian and patient’s oral or written assent obtained, if applicable and in 
accordance with the regulatory and legal requirements of the participating location 
4. Documented diagnosis of 5q SMA 
5. Diagnosed as later-onset (e.g., Type 2 or Type 3) SMA prior to receiving any treatment 
with therapy approved for SMA 
6. Nonambulatory patients must be able to sit independently (sits up straight with head erect 
for at least 10 seconds; does not use arms or hands to balance body or support position) 
per World Health Organization (WHO) motor milestones definition at Screening. Patients 
who never had the ability to walk independently will be classified as Type 2. Patients 
who previously had the ability to walk unaided will be classified as Type 3. 
7. Ambulatory patients must have the ability to independently ambulate without aids or 
orthotics over 10 meters at Screening 
8. For Cohort 1, RHS score no greater than 63 at Screening 
9. For Cohorts 2 and 3, HFMSE score no less than 10 at Screening 
10. Receiving the same background SMA therapy (e.g., on an approved SMN upregulator 
therapy such as nusinersen, or not on any SMA therapy) for at least 6 months prior to 
Screening and anticipated to remain on that therapy throughout the duration of the study 
a. If receiving the SMN upregulator therapy nusinersen, must have completed the 
loading regimen and initiated maintenance dosing (i.e., completed at least one 
maintenance dose) with at least 4 weeks after the first maintenance dose having 
elapsed prior to Screening 
11. Nutritional status stable over the past 6 months and anticipated to be stable throughout 
the duration of the study 
12. Have no physical limitations that would prevent the patient from undergoing motor 
function outcome measures throughout the duration of the study 
13. Able to receive study drug infusions and provide blood samples through the use of a 
peripheral IV, or a long-term IV access device that the patient has placed for reasons 
independent from the study (i.e., for background medical care and not for the purpose of 
receiving SRK-015 in the study), throughout the duration of the study 
14. Able to adhere to the requirements of the protocol, including travel to the study center 
and completing all study procedures and study visits 

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15. For patients who are expected to have reached reproductive maturity by the end of the 
study, adhere to study specific contraception requirements: 
a. Females of childbearing potential (see Section 10.1.7.4 for definition) must have a 
negative pregnancy test at Screening and agree to employ highly effective 
contraceptive measures (failure rate of 1% or less per year when used consistently 
and correctly) for the duration of the study and for 18 weeks following the last dose 
of study drug. Effective contraception methods are restricted to combined (estrogen 
and progestogen containing) hormonal contraception associated with inhibition of 
ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception 
associated with inhibition of ovulation (oral, injectable, implantable), intrauterine 
device, intrauterine hormone-releasing system, bilateral tubal occlusion, 
vasectomized partner, or sexual abstinence. In the context of this guidance, sexual 
abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study 
treatments. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient. 
b. Male patients with female partners of childbearing potential must be abstinent or 
agree to employ the use of a condom with or without spermicide throughout the 
duration of the study and for 18 weeks following the last dose of study drug. 
7.2. 
Patient Exclusion Criteria 
1. Use of tracheostomy with positive pressure 
2. Use of chronic daytime noninvasive ventilatory support for >16 hours daily in the 
2 weeks prior to dosing, or anticipated to regularly receive such daytime ventilator 
support chronically over the duration of the study 
3. Any acute or comorbid condition interfering with the well-being of the patient within 
14 days of Screening, including active systemic infection, the need for acute treatment or 
inpatient observation due to any reason 
4. Severe scoliosis and/or contractures at Screening. Based on clinical judgment, any 
scoliosis or contractures present must be stable over the past 6 months, anticipated to be 
stable for the duration of the study and not prevent the patient from being evaluated on 
any functional outcome measures throughout the duration of the study. 
5. Pregnant or breastfeeding 
6. Major orthopedic or other interventional procedure, including spine or hip surgery, 
considered to have the potential to substantially limit the ability of the patient to be 
evaluated on any functional outcome measures, within 6 months prior to Screening, or 
anticipated for the duration of the study 
7. Prior history of a hypersensitivity reaction to a mAb or recombinant protein bearing an Fc 
domain (such as a soluble receptor-Fc fusion protein), SRK-015, or excipients of 
SRK-015 
8. Use of systemic corticosteroids within 60 days prior to Screening. Inhaled or topical 
steroids are allowed. 

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9. Treatment with investigational drugs within 3 months or 5 half-lives, whichever is longer 
prior to Screening 
10. Use of therapies with potentially significant muscle effects (such as androgens, insulin-
like growth factor, growth hormone, systemic beta-agonist, botulinum toxin, or muscle 
relaxants or muscle-enhancing supplements) or potentially significant neuromuscular 
effects (such as acetylcholinesterase inhibitors) other than approved SMN upregulator 
therapy within 60 days prior to Screening 
11. Use of valproic acid within 60 days prior to Screening 
12. Patient has any other condition, which in the opinion of the Investigator may compromise 
safety or compliance, would preclude the patient from successful completion of the study, 
or interfere with the interpretation of the results 
7.3. 
Patient Withdrawal Criteria 
Patients may withdraw consent at any time. Participation in the study may be terminated at any 
time without the patient’s consent as determined by the Investigator. The Investigator may 
withdraw a patient from the study for any of the following reasons: 
• Protocol violation 
• Serious or intolerable AE (see Section 6.3.4) 
• Clinically significant change in a laboratory parameter (see Section 6.3.4) 
• Sponsor or Investigator decision 
• Patient and/or parent or guardian request 
7.4. 
Patient Rescreening, Replacement, and Over-enrollment 
A patient who is determined to be eligible based on screening assessments and experiences an 
acute or comorbid condition that causes a delay in their Baseline visit and first infusion (Day 0) 
may remain eligible up to an additional 14 days after the end of the Screening Period without 
having to rescreen. The patient may proceed with entering the Treatment Period after the 
resolution of the event and if deemed safe to do so by the Investigator. Screening patients who 
experience an acute clinical event that results in a delay of more than 14 days outside of the 
Screening Period must rescreen to determine eligibility. 
Patients who withdraw from the study for reasons that are not related to safety before receiving 
4 doses of SRK-015 and undergoing 2 postdose HFMSE or RHS assessments may be replaced at 
the discretion of the Sponsor. 
Patients who are in the Screening Period at the time a cohort has enrolled its required number of 
patients may continue to be enrolled after they are determined to be eligible. 
To preserve the robustness of the analyses, the Sponsor may enroll additional patients into a 
cohort as a result of patients in that cohort who significantly change their background approved 
SMA treatment while on study (e.g., a patient discontinues nusinersen or begins a new approved 
treatment as part of standard of care for their SMA). 

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7.5. 
Patient Enrollment into the Optional Extension Periods 
Patients who choose to enroll into Extension Period A should review and sign the informed 
consent form (ICF) prior to performing any assessments being conducted on Day 364 (V15). A 
patient is determined to be eligible for enrollment into Extension Period A after completion of 
the 52-week Treatment Period. Patients may consent to participate in Extension Period A at any 
time prior to V15/E1 or at V15/E1. 
Patients who choose to enroll into Extension Period B should review and sign the ICF prior to 
performing any assessments being conducted on Day 728 (EB1). A patient is determined to be 
eligible for enrollment into Extension Period B after completion of the 52-week Extension 
Period A. Patients may consent to participate in Extension Period B at any time prior to E14/EB1 
or at E14/EB1. 
Patients who choose to enroll into Extension Period C should review and sign the ICF prior to 
performing any assessments being conducted on Day 1092 (EC1). A patient is determined to be 
eligible for enrollment into Extension Period C after completion of the 52-week Extension 
Period B. Patients may consent to participate in Extension Period C at any time prior to 
EB14/EC1 or at EB14/EC1. 
 

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8. 
STUDY TREATMENT 
8.1. 
Study Drug Description 
SRK-015 drug product is a clear to slightly opalescent, colorless to slightly yellow solution, 
essentially free from visible particulates, containing 50 ± 5 mg/mL fully human anti-
proMyostatin mAb protein in 20 mM histidine, 130 mM sodium chloride, 0.02% polysorbate 80, 
at pH 6.0 in 1-mL solution. The drug product formulation does not contain novel excipients or 
excipients of animal origin. 
SRK-015 is a sterile, preservative-free liquid stored in a 6R clear, USP/EP Type I borosilicate 
glass vial with a 20 mm Flurotec®-coated, bromobutyl or chlorobutyl rubber stopper, and 20 mm 
crimp seal with a flip-off cap. SRK-015 is sterile filtered and filled to provide sufficient volume 
for withdrawal. Each vial is intended for single use administration only. SRK-015 is stable at 2 to 
8ºC. 
8.2. 
Study Drug Preparation and Administration 
Instructions for preparation of each IV dose of study drug will be provided to the Pharmacist. 
Preparation and dispensing of the study drug will be handled by the site pharmacy. Instructions 
for safe handling of the study drug are provided in the Pharmacy Manual. 
SRK-015 will be administered to patients at one of two dose levels: 20 mg/kg and 2 mg/kg, 
according to the cohort assignments. Doses will be diluted in normal saline and administered by 
IV over 2 hours (+10-minute window). If there are no acute reactions following the first 2 doses 
for a patient, and if the Investigator determines that it would be safe to do so, the infusion 
duration can be changed to less than 2 hours but no shorter than 1 hour. 
All doses will be administered via peripheral IV (or via long-term IV access device such as a 
peripherally inserted central catheter or port, if the patient has such a device for their background 
medical care). The placement of a new long-term IV access device is not part of this study, not 
required for participation, and should not be conducted if the only reason for it is to receive 
SRK-015. 
If an acute reaction occurs, further dosing will be suspended and the Investigator, in consultation 
with the Medical Monitor if needed, will evaluate the risk represented by the acute reaction. 
Such an evaluation will incorporate consideration of the nature of the event, relatedness to the 
drug, and seriousness and severity of the event. 
Intervention for patients who experience an acute infusion reaction should be performed in 
accordance with standard procedures and may include restarting the infusion at a slower rate, 
terminating the infusion, administration of medications, or other medically supportive measures, 
as necessary. 
8.3. 
Randomization and Blinding 
Cohorts 1 and 2 are directly assigned to the 20 mg/kg dose of SRK-015 while Cohort 3 patients 
will be randomized (1:1) in a double-blind manner to receive either 2 mg/kg or 20 mg/kg 
SRK-015 via an Interactive Web-based Randomization System (IWRS). Use of the IWRS will 
be outlined in the Study Operations Manual and in the IWRS quick reference guide. 

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The Sponsor, patients, caregivers, Investigators, and site personnel, with the exception of the 
Pharmacist, will be blinded to Cohort 3 SRK-015 dose level assignments as specified here. The 
site Pharmacist will remain unblinded throughout the duration of the study. The Sponsor will be 
blinded to individual efficacy data until prespecified interim analyses are performed (see 
Section 11.4). The Sponsor will remain blinded to efficacy data not included as part of the 
interim analyses until the Treatment Period database lock or deemed necessary by the SST. 
Select personnel of the Sponsor (e.g., Lead Clinical Research Associate and auditors) will have 
access to efficacy data to ensure study oversight. 
For unblinding procedures refer to Section 10.7.1.5. Based on interim analysis at 6 months 
(Day 168), which was supported by the 12-month analysis (Day 364), any Cohort 3 patients who 
were randomized to receive low-dose (2 mg/kg) SRK-015 will be re-assigned to receive 
high-dose (20 mg/kg) SRK-015 after completion of the Treatment Period (see Section 6.2). 
Original blind designation will be maintained. In accordance with Section 6.3.1, the SST reviews 
will not include any efficacy data. 
8.4. 
Study Drug Compliance 
Study drug will be administered under the supervision of the Investigator or qualified site 
personnel. The study site is required to adhere to all applicable laws, regulations, and guidelines 
including, but not limited to, the United States (US) Code of Federal Regulations (CFR), the 
International Council for Harmonisation (ICH) of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, the Health Insurance Portability and Accountability Act of 
1996, as well as any applicable local and federal regulations. 
8.5. 
Study Drug Packaging and Labeling 
Study drug will be supplied by Scholar Rock and packaged and labeled according to applicable 
local and regulatory requirements for investigational studies. 
8.6. 
Study Drug Storage and Accountability 
All supplies of SRK-015 must be stored refrigerated (2ºC to 8ºC/36ºF to 46ºF) in the carton and 
protected from light, in a securely locked area, and accessible to authorized persons only, until 
needed for dose preparation. 
The Investigator (or designee) is responsible for maintaining accurate accountability records of 
the investigational product throughout the clinical study. The site Pharmacist will inventory the 
investigational product received and will maintain records of disposition of the drug, including 
dates, quantity, and use. All dispensing and accountability records will be available for Sponsor 
review. Study drug accountability will be verified during on-site monitoring visits. At the end of 
the study, Study Monitors or designees will conduct a final accountability of all study drugs. 
8.7. 
Study Drug Disposal and Return 
Following accountability of study drug by a Study Monitor, used vials may be destroyed at the 
site according to local standard operating procedures (SOPs) containing well-documented 
destruction procedures. Unused vials should be returned to Scholar Rock, or its designated 
storage location, for final disposition. 

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8.8. 
Concomitant Treatment 
Concomitant treatment or interventional procedures that are medically indicated for any AEs the 
patient experiences during the study or that are provided as part of standard supportive care for 
the patient, is permitted at the discretion of the Investigator and supersedes any of the restrictions 
outlined in this protocol. 
Patients may receive an approved SMA treatment in accordance with the cohort they are enrolled 
into (Section 6.2). Patients are expected to remain on the same background SMA therapy 
(e.g., on an SMN upregulator therapy such as nusinersen, or not on any SMA therapy) for at least 
6 months prior to the first dose of study drug and throughout the duration of the study. 
Investigators who contemplate changing a patient’s standard of care treatment for their SMA are 
encouraged to discuss this with the Medical Monitor in advance. 
Patients that receive the SMN upregulator treatment, nusinersen, must receive their maintenance 
doses at least 24 hours after receiving SRK-015, or at least 14 days prior to any scheduled 
SRK-015 study drug administration visit. Any change in the timing of the patient’s nusinersen 
treatment that would fall within 14 days prior to the scheduled SRK-015 administration should 
be discussed with the Medical Monitor in advance. 
Investigational therapies are not permitted 3 months (or 5 half-lives, whichever is longer) prior to 
Screening and throughout the duration of the study. 
The concomitant use of the following drugs or products has the potential to interfere with the 
assessment of treatment effect in this study. Accordingly, the use of the following is prohibited 
from Screening through the final visit. 
• Live vaccinations within 14 days of any study visit where motor function outcome 
measures are conducted 
• Systemic corticosteroids. Inhaled and topical steroids are allowed. 
• Any therapy with potentially significant muscle effects (such as androgens, insulin-
like growth factor, growth hormone, systemic beta-agonist, botulinum toxin, muscle 
relaxants or muscle-enhancing supplements) or potentially significant neuromuscular 
effects (such as acetylcholinesterase inhibitors) other than approved SMN upregulator 
therapy 
• Valproic acid 

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9. 
ASSESSMENT OF EFFICACY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS 
9.1. 
Efficacy Endpoints 
Primary, secondary, and tertiary efficacy endpoints will be assessed at the times indicated in 
Table 2, Table 3, Table 4, and Table 5. The efficacy endpoints for each cohort are outlined in 
Table 7. Functional outcome measures (e.g., HFMSE/RHS, 6MWT, WHO Motor Milestones, 
RULM, 30-Second Sit-to-Stand, Endurance Shuttle Nine Hole Peg Test [ESNHPT], or 
Endurance Shuttle Box and Block Test [ESBBT]) will be conducted and assessed by the Physical 
Therapist. Requirements for the order of assessments, duration of assessments, and rest periods 
between assessments will be outlined in a separate Physical Therapist training manual. 
Study procedures will not be conducted for patients who develop an AE (e.g., musculoskeletal 
injury) during the study, irrespective of relatedness to study drug, that the Investigator considers 
would make it unsafe to perform a functional outcome assessment. Upon resolution of the AE, 
and if the Investigator assesses it would be safe to do so, performance of that study procedure 
will be resumed at the next scheduled assessment as indicated in Table 2, Table 3, Table 4, and 
Table 5. 
Table 7: 
Efficacy Endpoints by Cohort 
 
Cohort 1 
Cohorts 2 and 3 
Primary: 
Change from Baseline in the RHS 
total score at Day 364 (V15) 
Change from Baseline in the HFMSE total 
score at Day 364 (V15) 
Secondary: 
• 
Change from Baseline in the 
RHS total score at other 
prespecified timepoints 
• 
Proportion of patients achieving 
various magnitudes of change in 
RHS score from Baseline 
• 
Change from Baseline in the 
6MWT 
• 
Change from Baseline in the 
30-Second Sit-to-Stand 
• 
Change from Baseline in the 
10-Meter Walk/Run (from the 
RHS) 
• 
Change from Baseline in the 
timed rise from floor (from the 
RHS) 
• 
Change from Baseline in the HFMSE 
total score at other prespecified 
timepoints 
• 
Proportion of patients achieving various 
magnitudes of change in HFMSE score 
from Baseline 
• 
Change from Baseline in the RULM 
total score 
• 
Proportion of patients achieving various 
magnitudes of change in RULM from 
Baseline 
• 
Change from Baseline in the number of 
WHO motor development milestones 
attained 
• 
Proportion of patients who attain a new 
WHO motor development milestone 
relative to Baseline 

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Cohort 1 
Cohorts 2 and 3 
Tertiary: 
• 
Change from Baseline in the 
PEDI-CAT 
• 
Change from Baseline in the 
PROMIS Fatigue Questionnaire 
 
• 
Change from Baseline in time to 
limitation on the ESNHPT or ESBBT 
• 
Change from Baseline in the PEDI-
CAT 
• 
Change from Baseline in the PROMIS 
Fatigue Questionnaire 
Cohort 3 only: 
• 
Time to therapeutic effect (delineated in 
the SAP) as compared between low- 
and high-dose SRK-015 
6MWT = 6-Minute Walk Test; ESBBT = Endurance Shuttle Box and Block Test; ESNHPT = Endurance Shuttle 
Nine Hole Peg Test; HFMSE = Hammersmith Functional Motor Scale Expanded; PEDI-CAT = Pediatric Evaluation 
of Disability Inventory Computer Adaptive Test; PROMIS = Patient-reported Outcomes Measurement Information 
System; RHS = Revised Hammersmith Scale; RULM = Revised Upper Limb Module; SAP = statistical analysis 
plan; WHO = World Health Organization. 
9.1.1. 
Efficacy Parameters 
9.1.1.1. 
Revised Hammersmith Scale 
The RHS will be performed for the ambulatory patient subgroup (Cohort 1). Administration of 
the RHS includes the timed rise from floor and 10-Meter Walk/Run tests. The RHS is a 36-item 
clinical assessment for physical abilities of patients with Type 2 SMA, and ambulatory and 
nonambulatory patients with Type 3 SMA. The RHS includes 33 items that are graded on a scale 
of 0, 1, 2, where 0 denotes the lowest level of ability/function and 2 denotes the highest level of 
ability (Ramsey 2017). The remaining 3 items are scored 0, 1, where 0 denotes an inability and 
1 denotes an ability to achieve. The maximum achievable score is 69. 
9.1.1.2. 
10-Meter Walk/Run 
The 10-Meter Walk/Run test is an enhanced function of the RHS used for ambulant patients with 
Type 3 SMA. It is a measure of the time taken to walk/run 10 meters. 
9.1.1.3. 
Timed Rise from Floor 
The timed rise from floor test is an enhanced function of the RHS used for ambulant patients 
with Type 3 SMA. It is a measure of the time taken to rise to standing from the floor. 
9.1.1.4. 
6-Minute Walk Test 
The 6MWT is an assessment of exercise capacity and fatigue that has been used in clinical 
studies of ambulatory patients with later-onset SMA (Young 2016) Ambulant patients in 
Cohort 1 will complete the 6MWT. Patients are directed to walk along a 25-meter course as fast 
as possible over 6 minutes. The minute distances and total distance walked over 6 minutes is 
measured. 

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9.1.1.5. 
30-Second Sit-to-Stand 
The 30-Second Sit-to-Stand Test is used by researchers and clinicians as an assessment of 
functional lower limb strength (Jones 1999). The test was modified for ambulatory SMA 
population based on recent research of the modified 30-Second Sit-to-Stand being a reliable, 
feasible tool for use in a general geriatric population with a lower level of function (McAllister 
2019) and was related to fall risk in institutionalized veterans (Applebaum 2017, Le Berre 2016). 
The test measures the maximal number of times the patient can transition from sitting to standing 
in 30 seconds. 
9.1.1.6. 
Hammersmith Functional Motor Scale Expanded 
The HFMSE assesses the physical abilities of patients with Type 2 and Type 3 SMA (O'Hagen 
2007; Glanzman 2011) and will be performed for nonambulatory patient subgroups (Cohorts 2 
and 3). It consists of 33 items graded on a scale of 0, 1, 2, where 0 denotes unable, 1 denotes 
performed with modification or adaptation, and 2 denotes without modification or adaptation. 
9.1.1.7. 
Revised Upper Limb Module 
The RULM is a 20-item assessment of upper limb function in nonambulatory patients with SMA 
(young children as well as adults) (Mazzone 2017). The 19 scored items test functions that relate 
to everyday life, such as placing hands from lap, pressing a button, and picking up a token. The 
items are scored 0, 1, 2, where 0 denotes unable, 1 denotes able with modification, and 2 denotes 
able with no difficulty. The maximum score achievable is 37. Nonambulant patient subgroups 
(Cohorts 2 and 3) will perform the RULM. The RULM will be completed by patients who are 
30 months of age or older at the time of the baseline assessment. 
9.1.1.8. 
WHO Motor Development Milestones 
The WHO Multicentre Growth Reference Study performance criteria is being utilized to 
assess motor development milestones of patients with Type 2 and nonambulatory Type 3 
SMA enrolled in Cohort 2 and Cohort 3. 
9.1.1.9. 
Endurance Shuttle Nine Hole Peg Test 
The ESNHPT is an endurance test for severely affected patients with SMA. Patients are 
instructed to repeatedly perform the original 9 Hole Peg Test at 75% of their individual 
maximum speed. The shuttles refer to the set speed marked by auditory cues, with the test ending 
when the patient missed 2 consecutive beeps. The primary outcome parameter is “time to 
limitation (Tlim),” which is defined as the time a task can be maintained at the pre-set intensity. 
Maximum test duration is 20 minutes (Stam 2018). Nonambulant patients who score ≤3 on 
Item A of the RULM at Screening will perform the ESNHPT at Screening and all subsequent 
assessments. The ESNHPT will be completed by patients who are or will turn 8 years of age or 
older during the study. Patients who turn 8 years of age in Extension Periods A, B, or C who 
score ≤3 on Item A of the RULM at Screening should perform the ESNHPT as early as possible 
(preferred to begin at E1) and at all subsequent assessments until the end of the study. 

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9.1.1.10. Endurance Shuttle Box and Block Test 
ESBBT is an endurance test for moderately affected patients with SMA. Patients are instructed 
to repeatedly perform the original Box and Block Test at 75% of their individual maximum 
speed. The shuttles refer to the set speed marked by auditory cues, with the test ending when the 
patient missed 2 consecutive beeps. The primary outcome parameter is Tlim. Maximal test 
duration is 20 minutes (Stam 2018). Nonambulant patients who score >3 on Item A of the 
RULM at Screening will perform the ESBBT at Screening and all subsequent assessments. The 
ESBBT will be completed by patients who are or will turn 8 years of age or older during the 
study. Patients who turn 8 years of age in Extension Periods A, B, or C who score >3 on Item A 
of the RULM at Screening should perform the ESBBT as early as possible (preferred to begin at 
E1) and at all subsequent assessments until the end of the study. 
9.1.1.11. Pediatric Evaluation of Disability Inventory Computer Adaptive Test 
A caregiver (who may or may not be a parent and/or legal guardian) must complete the PEDI-
CAT Assessment. The PEDI-CAT Assessment should not be administered if a caregiver is not 
present. The PEDI-CAT Assessment should not be administered to the patient. The PEDI-CAT 
is a questionnaire completed by the caregiver that assesses the patient’s ability to perform daily 
functions (Haley 2005). The PEDI-CAT is filled out by the caregiver in a location where they are 
not watching the patient perform any functional assessment tests. The same caregiver must fill 
out the assessment throughout the study duration. The answers are scored on a 4-point scale 
(unable to easy). The test is suitable to assess function in newborns to 21-year-olds; this 
questionnaire should be completed throughout the duration of the study (regardless of age). 
Properties of the PEDI-CAT have been studied in the SMA population. A Rasch analysis with 
results published in 2016 revealed that the distribution of abilities for the Mobility and Daily 
Activities domains of the PEDI-CAT are best represented in the Type 2 and Type 3 populations 
(Pasternak 2016). As the PEDI-CAT is an age-dependent questionnaire, a patient’s full date of 
birth is required for accurate assessment. 
9.1.1.12. Patient-reported Outcomes Measurement Information System 
The Patient-reported Outcomes Measurement Information System (PROMIS) is a person-
centered measure intended to be completed by the patient or parent proxy without help from 
anyone (Ader 2007). The fatigue profile domain measures a range of symptoms, from mild 
subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of 
exhaustion. The self-report measures are suitable for children 8-17 years old and the parent 
proxy report measures are suited for children 5-17 years old. If a caregiver completes this form, 
the same caregiver must complete the form throughout the study duration. Patients age 
18 through 21 years old will complete an adult form of PROMIS. The PROMIS will be 
completed by patients who are or will turn 5 years of age or older at the time of the baseline 
assessment; the same questionnaire used at Screening should be used throughout the duration of 
the study (regardless of age). 
9.2. 
Pharmacokinetics Blood Sample Collection 
Blood samples for the measurement of SRK-015 concentrations will be obtained prior to study 
drug infusion as indicated in the schedule of assessments in Table 2, Table 3, Table 4, and 

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Table 5. In the Treatment Period, the 2-hour (± 1 hour) postdose (from the stop of the infusion) 
sample collection on Day 0, Day 140, and Day 336 must be collected via peripheral 
venipuncture. In Extension Periods A, B, and C, the 1-hour (+30-minute window) postdose 
(from the stop of the infusion) sample collection on Day 700, Day 1008, Day 1092, and 
Day 1428 must be collected via peripheral venipuncture. 
Each collected sample will be split into approximately equal volume sample sets to allow for 
retesting, if required. Aliquots from the PK blood samples may be used for biomarker testing 
(Extension Period C only) or additional PD or immunogenicity testing as appropriate, and 
Baseline and postbaseline samples may be used to support PK, PD, and/or ADA assay 
validation. 
9.3. 
Pharmacodynamics Blood Sample Collection 
Blood samples will be collected for the measurement of latent myostatin levels. These blood 
samples will be obtained prior to infusion as indicated in the schedule of assessments in Table 2, 
Table 3, Table 4, and Table 5. The 2-hour (+30-minute window) postdose (from stop of infusion) 
sample collection on Day 0 must be collected via peripheral venipuncture. Each collected sample 
will be split into approximately equal volume sample sets to allow for retesting, if required. 
Aliquots from the PD blood samples may be used for biomarker testing (Extension Period C 
only) or additional PK or immunogenicity testing as appropriate, and Baseline and postbaseline 
samples may be used to support PK, PD, and/or ADA assay validation. 
9.4. 
Immunogenicity Blood Sample Collection 
Blood samples for the measurement of anti-SRK-015 antibodies will be obtained prior to 
infusion as indicated in the schedule of assessments in Table 2, Table 3, Table 4, and Table 5. 
Each collected sample will be split into approximately equal volume sample sets to allow for 
retesting, if required. Aliquots from the immunogenicity samples may be used for biomarker 
testing (Extension Period C only) or additional PK or PD testing as appropriate, and Baseline and 
postbaseline samples may be used to support PK, PD, and/or ADA assay validation. 
9.5. 
Biomarkers (Extension Period C Only) 
Aliquots from PK, PD, and ADA serum samples collected during Extension Period C will be 
stored and may be used for exploratory biomarker testing. These samples may be used for 
research to develop methods, assays, prognostics, and/or companion diagnostics related to 
discovering and/or evaluating effects of SRK-015. Additional blood samples will not be 
collected for the purposes of biomarker testing. 

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10. 
ASSESSMENT OF SAFETY 
10.1. 
Safety Parameters 
10.1.1. 
Demographic/Medical History 
Patient demographics and medical history will be recorded on the source document and 
electronic case report form (eCRF). Demographic characteristics include age, sex, race, and 
ethnicity. Medical history will capture the patient’s SMA history as well as current and past 
relevant medical status (surgeries, allergies, and concomitant medications). 
10.1.2. 
Vital Signs 
Vital signs will be performed by the Investigator or his/her qualified designee according to the 
schedule of assessments provided in Table 2, Table 3, Table 4, and Table 5. Routine vital sign 
assessments will include heart rate, blood pressure, and respiratory rate to be collected in the 
Treatment Period at preinfusion, every 15 minutes (±5 minutes) during the infusion from the 
start of the infusion, at the end of the infusion, and 1 and 2 hours (±15 minutes) postinfusion. In 
Extension Periods A, B, and C, vital sign assessments will be collected at preinfusion, every 
15 minutes (±5 minutes) during the infusion (from the start of the infusion), at the end of the 
infusion, and 1 hour (±15 minutes) postinfusion. Body temperature will be collected preinfusion. 
10.1.3. 
Weight and Height 
Weight and height will be collected according to the schedule of assessments provided in 
Table 2, Table 3, Table 4, and Table 5. Weight will be collected within 48 hours of each dose to 
calculate weight-based dosing and height will be collected at visits where the motor function 
outcome measures are conducted. Standing height will be collected for all individuals who are 
able to independently stand. Surrogate height may be estimated using ulna length if the patient is 
nonambulatory or needs standing support. 
10.1.4. 
Physical Examination 
A complete physical examination will be performed by the Investigator or a qualified designee 
according to the schedule of assessments provided in Table 2, Table 3, Table 4, and Table 5. The 
findings of each examination will be recorded on the source documents and eCRF. The physical 
examination will include an assessment of the following: general appearance, skin, lymph nodes, 
head-eyes-ears-nose-throat, neck, abdomen, extremities, and the respiratory, cardiovascular, 
musculoskeletal, and neurologic body systems. 
10.1.5. 
Electrocardiogram 
A 12-lead electrocardiogram (ECG) will be collected at the times indicated in Table 2, Table 3, 
Table 4, and Table 5. ECGs are to be performed with the patient having rested for at least 
5 minutes before each reading. ECGs are to be performed in triplicate, each at least 1 to 
2 minutes apart. On infusion days, ECG will be collected within 2 hours prior to the start of the 
infusion and within 1 hour after the end of infusion at Visits EC1 and EC13. ECGs will be sent 
to a central reading vendor for assessment. 

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10.1.6. 
Concomitant Medications 
All concomitant medications will be collected from the time the patient signs the ICF through 
12 weeks after the final dose. 
10.1.7. 
Laboratory Assessments 
Laboratory testing (eligibility screening, serum chemistry, hematology, urinalysis, and 
coagulation, PK and PD sample draw, and ADA testing) will be performed using established 
methods at the times indicated in Table 2, Table 3, Table 4, and Table 5. When multiple sample 
collection types are performed at the same assessment time point, the samples will be drawn in 
the following order (depending on what sample types are to be collected at that time point): 
laboratory safety samples (hematology, coagulation, serum chemistry, urinalysis), PK, PD, 
ADAs. Aliquots from the PK, PD, and ADA samples may be retained as back-up for retesting if 
necessary. The total blood draw for each patient who completes the 52-week Treatment Period, 
will be approximately 158 mL. Patients who do not enroll into Extension Period A and complete 
the 12-week Safety Follow-up Period will have approximately 25 mL of additional blood drawn. 
The total blood draw for each patient who completes the 52-week Extension Period A, will be 
approximately 82 mL. Patients who do not enroll into Extension Period B and complete the 
12-week Safety Follow-up Period will have approximately 13 mL of additional blood drawn. 
The total blood draw for each patient who completes the 52-week Extension Period B will be 
approximately 77 mL. Patients who do not enroll into Extension Period C and complete the 
12-week Safety Follow-up Period will have approximately 13 mL of additional blood drawn. 
The total blood draw for each patient who completes the 52-week Extension Period C will be 
approximately 57 mL. Patients who do not enroll into the separate long-term safety extension 
and complete the 12-week Safety Follow-up Period will have approximately 13 mL of additional 
blood drawn. 
Please refer to the Laboratory Manual for more information. 
10.1.7.1. Hematology and Coagulation 
The following hematology and coagulation parameters will be assessed: 
• Hemoglobin 
• Red blood cell count 
• Hematocrit 
• White blood cell count with differential 
• Absolute platelet count 
• Mean corpuscular hemoglobin 
• Mean corpuscular hemoglobin concentration 
• Mean corpuscular volume 
• Activated partial thromboplastin time (APTT) 
• Prothrombin time/international normalized ratio (PT/INR) 

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10.1.7.2. Blood Chemistry 
The following blood chemistry parameters will be assessed: 
• Albumin 
• Alanine aminotransferase 
• Alkaline phosphatase 
• Aspartate aminotransferase 
• Bilirubin (total and direct) 
• Blood urea nitrogen 
• Calcium 
• Carbon dioxide 
• Chloride 
• Creatinine 
• Creatine phosphokinase 
• Gamma-glutamyl transferase 
• Glucose  
• Pregnancy (females only) 
• Lactate dehydrogenase 
• Magnesium 
• Phosphate 
• Potassium 
• Sodium 
• Total cholesterol 
• Total protein 
• Triglycerides 
• Uric acid 
10.1.7.3. Urinalysis 
The following urinalysis parameters will be assessed: 
• Bilirubin 
• Blood microscopy (if urinalysis is 
abnormal) 
• Glucose 
• Ketones 
• Nitrite 
• pH 
• Protein 
• Specific gravity 
10.1.7.4. Pregnancy Testing 
A female is considered of childbearing potential, following menarche and until becoming 
postmenopausal unless permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is 
defined as no menses for 12 months without an alternative medical cause. 
Pregnancy testing will be conducted for females of childbearing potential at the times indicated 
in Table 2, Table 3, Table 4, and Table 5. A urine or serum test is acceptable however, positive 
urine tests must be confirmed with serum testing. 
Patients who become pregnant during the study should not receive further study drug and should 
be followed according to the procedures outlined in Section 10.7.1.3. 

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10.2. 
Adverse and Serious Adverse Events 
10.2.1. 
Definition of Adverse Events 
10.2.1.1. Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical study patient administered a 
pharmaceutical product that does not necessarily have to have a causal relationship with the 
treatment administered. An AE can, therefore, be any unfavorable or unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not related to the medicinal product. 
• AEs may be new events or may be preexisting conditions that have become 
aggravated or have worsened in severity, seriousness, or frequency from Baseline at 
any time during the study. 
• AEs may be clinically significant changes from Baseline in physical examination, 
laboratory tests, or other diagnostic investigation. 
Any medical condition already present at Screening should be recorded as medical history and 
not be reported as an AE unless the medical condition or signs or symptoms present changes in 
severity, frequency, or seriousness at any time during the study. In this case, it should be reported 
as an AE. 
10.2.1.2. Serious Adverse Event 
An SAE is any adverse experience occurring at any dose that results in any of the following 
outcomes: 
• Death 
• Life-threatening experience; Note: “Life-threatening” refers to a situation in which 
the patient was at immediate risk of death at the time of the event; it does not refer to 
an event that might have caused death if it were more severe. 
• Inpatient hospitalization or prolongation of existing hospitalization. The following are 
excluded as per this criterion: 
− Emergency room visits/hospital admissions for AEs less than 24 hours in duration 
do not meet SAE criterion unless they meet any of the other SAE criteria in this 
list. 
− A scheduled or elective hospitalization for medical/surgical procedure planned 
prior to informed consent for a preexisting condition that has not worsened from 
Baseline during participation in the study. However unexpected complications 
and/or prolongation of hospitalization that occur during elective surgery should be 
recorded as AEs and assessed for seriousness. Admission to the hospital for social 
or situational reasons (i.e., no place to stay, too far away to come for hospital 
visits, respite care) will not be considered inpatient hospitalizations. 
• Persistent or significant disability or incapacity or substantial disruption of the ability 
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• Congenital anomaly or birth defect 
• Is considered to be an important medical event: Important medical events are those 
that may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the patient or may require intervention to prevent one of the outcomes 
listed in the definition above. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalizations, or the 
development of drug dependency. 
10.2.1.3. Dosing Errors 
All dosing errors (including, but not limited to, route of administration and wrong dose) must be 
reported as protocol deviations. A brief description should be provided in the deviation report, 
including information about whether the patient was symptomatic or not. Dosing details should 
be captured in the eCRF. 
An overdose is defined as a significant variation from the recommended/scheduled dosage for a 
product. The dosing for this study will be conducted in a controlled clinical setting and an 
overdose is not anticipated. However, in the event of an accident, for this study, an overdose of 
SRK-015 is considered a dose that is at least 2-fold higher than 20 mg/kg. 
Overdoses are not considered AEs and should not be recorded as an AE in the eCRF unless an 
AE or an SAE occurs. All overdoses (regardless of whether or not they result in an AE) must be 
recorded in the eCRF. If an overdose results in an SAE, the SAE form must be completed and 
faxed to Scholar Rock or designee (e.g., PPD). Should an overdose occur, the Investigator or 
designee must contact the Medical Monitor within 24 hours. 
10.2.1.4. Pregnancy 
Pregnancy is not an AE; however, if a female patient or female partner of a male study patient 
becomes pregnant during the conduct of the study, the Investigator must notify PPD according to 
the procedures provided in Section 10.7.1.3. A patient becoming pregnant while on study drug 
will immediately be withdrawn from further dosing and will be followed according to the 
procedures provided in Section 10.7.1.3. 
10.2.1.5. Treatment-Emergent Adverse Event 
An AE is treatment emergent if the onset time is after administration of the first dose of study 
drug through the final follow-up visit or, in the event that onset time precedes study drug 
administration, the AE increases in severity during the Safety Follow-up Period. 

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10.3. 
Adverse Event Monitoring 
Each patient will be monitored for the occurrence of AEs, including SAEs, from the signing of 
the ICF through the final follow-up visit. 
• Patients will be questioned and/or examined by the Investigator or a qualified designee 
for evidence of AEs. The questioning of patients with regard to the possible occurrence 
of AEs will be generalized such as, “How have you been feeling since your last visit?” 
The presence or absence of specific AEs should not be elicited from patients. 
• Patients having AEs will be monitored until resolution or stabilization (in the case of 
persistent impairment), or until the event becomes chronic in nature, or the patient dies. 
• AEs, actions taken as a result of AEs, and follow-up results must be recorded in the eCRF 
as well as in the patient's source documentation. Follow-up laboratory results should be 
filed with the patient's source documentation. 
For any SAEs or AEs that require the patient to be discontinued from dosing, relevant clinical 
assessments and laboratory tests will be repeated as clinically appropriate, until final resolution 
or stabilization of the event(s). Patients will continue to be followed through 12 weeks after the 
final dose. 
All safety laboratory analyses will be performed at a central laboratory. The clinical laboratory 
values will be reported to the Investigator who will review them for clinical significance and 
consideration of abnormal values as potential AEs. 
10.3.1. 
Relationship to Study Drug (Causality Assessment) 
A medically qualified Investigator must assess the relationship of any AE (including SAEs) to 
the use of the investigational product, as related or not related, based on clinical judgment and 
using all available information, and may include consideration of the following factors: 
• The temporal sequence from study drug administration 
• Underlying, concomitant, intercurrent diseases 
• Concomitant use of other drugs 
• Whether the manifestations of the AE are consistent with known actions or toxicity of 
the investigational product 
• Exposure to physical and/or mental stresses 
• The pharmacology and PK of the study drug 
• The AE resolved or improved with decreasing the dose or stopping the use of the 
investigational product (dechallenge). Judgment should be used if multiple products 
are discontinued at the same time. 
The causal relationship between the study drug and the AE will be assessed using one of the 
following categories: 
• Not Related: Factors consistent with an assessment of Not Related may include: 
− Temporal relationship is lacking (e.g., the event did not occur within a reasonable 
time frame following administration of the study drug); or 

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− Other causative factors more likely explain the event (e.g., a preexisting 
condition, other concomitant medications) 
• Related: Factors consistent with an assessment of Related may include: 
− There is a positive temporal relationship (e.g., the event occurred within a 
reasonable time frame following administration of study drug) 
− The AE is more likely explained by the investigational product than by another 
cause (e.g., the AE shows a pattern consistent with previous knowledge of the 
investigational product or the class of the investigational product). 
10.4. 
Assessment of Expectedness 
As part of the regulatory reporting requirements, the Sponsor must perform an assessment of 
expectedness (expected/unexpected from the perspective of previously observed, not on the basis 
of what might be anticipated from the pharmacological properties of a medicinal product) for 
AEs. Adverse reactions will be considered unexpected if the nature, seriousness, severity or 
outcome of the reaction(s) is not consistent with the reference safety information section of the 
Investigator’s Brochure. 
10.5. 
Common Terminology Criteria for Adverse Events 
Clinical and laboratory AEs will be graded using the National Cancer Institute Common 
Terminology Criteria for Adverse Events, Version 5.0. 
The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe nausea). This is not the same as “serious,” which is based 
on patient/event outcome or action criteria usually associated with events that pose a threat to a 
patient’s life or functioning. 
10.6. 
Recording Adverse Events 
Each patient will be monitored for the occurrence of AEs, including SAEs, from the signing of 
the ICF through the final follow-up visit. Patients and/or their legal guardians will be questioned, 
and the patients may be examined by the Investigator or a qualified designee for evidence of 
AEs. Patients having AEs will be monitored with relevant clinical assessments and laboratory 
tests, as determined by the Investigator. 
For each AE, the Investigator will evaluate and record the requested information in the eCRF and 
the patient’s source documentation. 
10.6.1. 
Instructions for Recording AEs in eCRF 
10.6.1.1. Recording Diagnosis Versus Signs and Symptoms 
If a patient reports signs and symptoms that represent a medical diagnosis/syndrome, the final 
diagnosis/syndrome should be recorded in the eCRF rather than each sign and symptom 
(e.g., cough, runny nose, fever = upper respiratory infection). However, if a medical diagnosis 
cannot be made, then each sign or symptom should be recorded as an individual SAE or AE, as 
appropriate. 

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10.6.1.2. Abnormal Laboratory Values or Vital Signs 
Protocol defined laboratory values and vital signs should not be reported as AEs unless the 
abnormal laboratory value or vital sign meets at least one of the following: 
• Requires an adjustment in the study drug(s) or discontinuation of treatment; 
• Requires medical or surgical intervention; 
• Is associated with accompanying signs/symptoms that are not considered part of a 
preexisting diagnosis or syndrome (or if considered part of a preexisting diagnosis or 
syndrome, is associated with disease worsening); or 
• Is considered clinically significant by the Investigator, 
10.7. 
Reporting Serious Adverse Events 
10.7.1. 
Serious Adverse Event Reporting 
10.7.1.1. Initial Reports 
All SAEs occurring from the time of informed consent through the final study visit must be 
reported to PPD within 24 hours of the awareness of the occurrence (this refers to any AE that 
meets any of the aforementioned serious criteria). (Note: The change in reporting from Medpace 
to PPD became effective on 20 May 2021). All SAEs that the Investigator considers related to 
study drug occurring after the study must be reported to the Sponsor. 
To report the SAE, the SAE form will be completed electronically in the electronic data capture 
(EDC) system for the study. When the form is completed, PPD Safety personnel will be notified 
electronically and will retrieve the form. Any supporting documentation (e.g., discharge 
summary, diagnostic results) must be redacted by the site and emailed or faxed to PPD (contact 
information below). 
If the EDC system cannot be accessed for technical reasons and the event meets serious criteria, 
complete the back-up paper SAE form and send via email or fax to PPD (contact information 
below) or call the PPD SAE reporting line (phone number listed below). When the EDC system 
becomes available, the SAE information must be entered within 24 hours of the system 
becoming available. 
Safety Contact Information: PPD 
PPD SAE reporting line – USA/Canada: 
Telephone: +1.888.483.7729 
Fax: +1.888.529.3580 
PPD SAE Hotline – Europe: 
Telephone: +44 122 337 4240 
Fax: +44 122 337 4102 
Email: RTPSafety@ppd.com 

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10.7.1.2. Follow-up Reports 
The Investigator is required to follow SAEs until resolution, stabilization (in the case of 
persistent impairment), or until the event becomes chronic in nature, or the patient dies. SAE 
resolution is defined as: 
• Resolved with or without residual effects 
• A return to Baseline for a preexisting condition 
• Laboratory values have returned to Baseline or stabilized 
• The Investigator does not expect any further improvement or worsening of the event 
• Fatal outcome - if an autopsy is performed, the autopsy report should be provided to 
the Sponsor as soon as it is available. 
Within 24 hours of receipt or awareness of follow-up information, the Investigator must update 
the SAE form electronically in the EDC system for the study and submit any supporting 
documentation (e.g., patient discharge summary or autopsy reports) to PPD\ via fax or email. All 
supporting patient documentation must be redacted for personal details as per Good Clinical 
Practice (GCP). If it is not possible to access the EDC system, refer to the procedures outlined 
above for initial reporting of SAEs. 
10.7.1.3. Reporting Pregnancies 
If a female patient or the female partner of a male patient becomes pregnant during the course of 
the study, the Investigator must report the pregnancy to PPD within 24 hours of awareness of the 
event. PPD will then forward the paper exposure in utero (EIU) form to the Investigator/site for 
completion. The Investigator/site must complete the EIU form and fax/email it back to PPD 
within 24 hours. The Investigator/site must obtain consent to collect pregnancy information 
(including the status of the newborn, if applicable). 
The patient or partner should be followed by the Investigator until completion of the pregnancy, 
whenever possible. Once the outcome of the pregnancy is known, the follow-up EIU form should 
be completed and faxed/emailed to PPD within 24 hours. At the completion of the pregnancy, 
the Investigator will document the outcome of the pregnancy. If the outcome of the pregnancy 
meets the criteria for immediate classification as an SAE (i.e., postpartum complication, 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly), the Investigator should 
follow the procedures for reporting an SAE. 
Refer to Section 10.7.1.1 for Safety Contact Information. 
10.7.1.4. Reporting to Institutional Review Board/Independent Ethics Committee by 
Investigator 
The Investigator is responsible to report any expedited reports to their local IRB or IEC, per local 
reporting regulations. 

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10.7.1.5. Unblinding a Patient’s Treatment During the Study 
Treatment Period: 
In the event of a drug-related, serious, unexpected AE, Scholar Rock will provide the Cohort 3 
patient’s dose level for the purpose of regulatory authority agency reporting, if appropriate. 
Because all patients in the study receive SRK-015, unblinding of a Cohort 3 patient’s dose level 
(i.e., high vs. low dose) by the Investigator is discouraged. In the event of a drug-related SAE, 
the Investigator may, if deemed medically necessary to provide patient care, and after 
consultation with the Medical Monitor, obtain the patient’s dose level from the IWRS system. 
Extension Periods: 
Any Cohort 3 patients who were randomized to receive low-dose (2 mg/kg) SRK-015 will be 
re-assigned to receive high-dose (20 mg/kg) SRK-015 after completion of the Treatment Period 
(see Section 6.2). As of Protocol Version 5.0, unblinding is no longer applicable because all 
Cohort 3 patients randomized to the low dose who enrolled in Extension Period A have switched 
to the high dose. 
10.7.2. 
Expedited Reporting by the Sponsor to a Regulatory Health Authority 
The Sponsor/designee will manage the expedited reporting of relevant safety information to 
concerned health authorities in accordance with local laws and regulations. The 
Sponsor/designee will also inform all Investigators as required per local regulation. 

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11. 
STATISTICS 
11.1. 
General Methodology 
All analyses will be performed under GCP standards using a prospective SAP. Analyses will be 
conducted using Statistical Analysis System (Version 9.4 or later, Cary, North Carolina). 
The study is regarded as 3 separate cohorts; therefore, no Type I error is allocated towards 
separate cohort testing. No formal statistical testing will be applied for the interim analysis and 
no alpha spending will be applied. Two-sided 95% confidence intervals (CIs) will be reported. 
There will be an interim analysis conducted when prespecified enrollment (see below) and 
treatment duration have been reached for all 3 cohorts (see Section 11.4); the final analysis will 
be conducted once each cohort completes the 52-week Treatment Period. Biostatistics Data 
Review Meetings will be held for the final analyses to distinguish between major and minor 
protocol violations. Both Per-Protocol and Intention-to-Treat (ITT) populations will be analyzed, 
with the ITT population being the primary analysis population. 
Any changes in the analysis as specified in the protocol will be delineated in the SAP. 
11.2. 
Analysis Strategy 
All prespecified safety and efficacy endpoints will be analyzed by cohort and by dose group for 
Cohort 3. All patients with any postbaseline data will be included in the interim and primary 
analyses. In addition, safety and efficacy data for the high dose will be analyzed for different 
cohort/dose combinations taking cohort, dose level, and receiving background SMA therapy into 
consideration. For the change from Baseline analyses (to utilize the patient as their own control 
for response analyses), the last observation before the first dose will be used as the Baseline. 
Cohort 3 low- vs high-dose treatment outcomes will also be evaluated for the time to response as 
a descriptive outcome. 
11.2.1. 
Safety Analyses 
Safety data will be evaluated for vital signs, laboratory outcomes, concomitant medications, 
ECGs, and AEs. Clinically significant outcomes will be noted. Vital signs and laboratory 
outcomes will be summarized within each treatment group within all cohorts and the 2 dose 
groups within Cohort 3. AEs will be coded in the Medical Dictionary for Regulatory Activities; 
the emphasis will be on treatment-emergent adverse events (TEAEs); the TEAE type, incidence, 
severity, relationship, onset and resolution time will be displayed descriptively. The incidence 
rate of AEs and TEAEs will be reported. 
11.2.2. 
Efficacy Analyses 
Efficacy data will be evaluated for multiple measures with continuous endpoints (e.g., HFMSE 
score, RHS score, RULM score, etc.) at time points specified in Table 2, Table 3, Table 4, and 
Table 5. The primary endpoints and other efficacy continuous endpoints will be summarized 
within cohorts and by dose groups for Cohort 3; corresponding two-sided 95% CIs will be 
computed as well. Similar analyses for different cohort/dose combinations will be explored. The 
HFMSE, RHS, and WHO motor development endpoints will be further categorized to assess the 

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specific distributions of the change from Baseline (waterfall displays of unit changes from 
Baseline) and the proportion of patients reaching certain milestones. 
Waterfall charts will be generated to display the distribution of improvement from Baseline for 
HFMSE, RHS, RULM, and other unit-based measures at postbaseline milestones in support of 
efficacy and future study planning. 
Time to outcome improvement will be assessed using Kaplan-Meier lifetables to characterize 
time to efficacy for Cohort 3 low dose versus high dose. 
11.2.3. 
Pharmacokinetic and Pharmacodynamic Analysis 
All patients who receive at least 1 dose of study drug and have at least 1 quantifiable PK result 
will be included in the population PK analysis. The data from this study may be combined with 
other Sponsor SMA studies for both population PK analysis and exposure-response analysis, if 
data permit. SRK-015 concentrations and circulating latent myostatin concentrations will be 
determined using blood samples collected before and after dosing through the final follow-up 
visit. SRK-015 concentrations will be listed and summarized in tabular formats using descriptive 
statistics and will be plotted against time points by cohort, and dose and schedule. The latent 
myostatin concentrations will be listed for each patient and summarized by cohort. 
11.2.4. 
Anti-SRK-015 Antibody Analysis 
All patients who receive at least 1 dose of study drug and have at least 1 ADA result will be 
included in the immunogenicity evaluation. The ADA population is defined as patients who 
receive at least 1 dose of study drug and have a pretreatment result and at least 1 posttreatment 
result from the ADA sample collection. Immunogenicity will be evaluated through a 3-tier ADA 
assay (screening, confirmatory, and titer) and a neutralizing antibody assay. The number and 
percent of patients who become positive for ADAs and who develop neutralizing antibodies will 
be listed and summarized in tabular format using descriptive statistics by cohort, visit, dose and 
schedule, and overall. 
11.3. 
Sample Size Rationale 
Sample sizes for each cohort were based on practical considerations. Sample sizes of 15 to 
20 patients for each cohort will provide 80% power to reject the null hypothesis involving mean 
changes from Baseline within each treatment group relative to prespecified alternative 
hypothesis using a paired t-test with two-sided 5% Type 1 error. Table 8 presents the effect sizes 
within dose groups that can be detected with 80% power and two-sided 5% Type I error as well 
as the effect sizes that will reject the null hypothesis of no difference according to two-sided 
p=0.05. As illustration, assuming a 2.5-unit standard deviation (SD) for the change from 
Baseline for HFMSE, a mean 1.7-unit improvement for HFMSE (n=20) and a mean 2-unit 
improvement for HFMSE (n=15) can be detected with 80% power while a mean 1.2-unit 
improvement in HFMSE (n=20) and a mean 1.3-unit improvement in HFMSE reaches two-sided 
p=0.05 (rules out a 0 as the two-sided 95% CI for the change from Baseline). 
 

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Table 8: 
Paired T-test: Reject Null Hypothesis No Mean Change from Baseline 
  
80% Power 
Two-sided p=0.05 
Test significance level, α 
0.05 
0.05 
0.05 
0.05 
Effect size, e = |∆1 - ∆2| / s 
0.66 
0.778 
0.462 
0.543 
n (after losses) 
20 
15 
20 
15 
In addition, the total sample size for Cohort 3 (n= 20) provides 80% power to reject the null 
hypothesis of no mean change from Baseline against the prespecified difference between doses 
for a clinically meaningful improvement at a two-sided 5% Type I error for a 1:1 randomization 
(high dose vs. low dose). 
Table 9 presents the effect size which could be detected with 80% power and a two-sided 5% 
Type 1 error as well as the effect sizes required to reject the null hypothesis of no change from 
Baseline for comparing Cohort 3 low vs. high dose. If the SD of the change from Baseline is 
2.5 units for HFMSE, then a mean 2.4-unit difference between low and high dose will reach 
two-sided p=0.05 (rules out 0 as the lower two-sided 95% CI as the mean difference between 
dose groups). 
Table 9: 
Unpaired T-test: Reject Null Hypothesis: No Mean Difference from Baseline 
  
80% Power 
Two-sided p=0.05 
Two-sided significance level, α 
0.05 
0.05 
Effect size, e = |∆A - ∆o| / s 
1.325 
0.926 
n per group (after losses) 
10 
10 
11.4. 
Interim Analyses 
11.4.1. 
Pharmacokinetic and Pharmacodynamic Interim Analysis 
Prespecified interim analyses to initially evaluate drug exposure (i.e., PK) and target engagement 
(i.e., PD) in patients with SMA will be conducted. For Cohorts 1 and 2, these analyses will be 
conducted after approximately 4 patients in each cohort have received at least 2 doses of 
SRK-015. For Cohort 3, these analyses will be conducted after approximately 6 patients have 
received at least 2 doses of SRK-015. Data from multiple cohorts may be combined as necessary. 
Enrollment will continue while the interim analysis is ongoing. Based on these results, and 
taking into consideration any available safety data, the cohort-specific dose levels may be 
adjusted. Any adjustment in dose level will not change the frequency of dosing (i.e., every 
4 weeks) and the highest dose will not exceed 30 mg/kg, as tested in the Phase 1 study. 
11.4.2. 
Safety and Efficacy Interim Analyses 
Prespecified interim analyses to evaluate the initial safety and efficacy of SRK-015 in patients 
with SMA will be conducted when all enrolled patients complete Day 168 (Visit 8) or are 
terminated from the study. Interim analyses will be performed on the efficacy endpoints in 
addition to all safety outcomes and available PK and PD results. Safety data at all visits and 
efficacy endpoints at Day 168 (Visit 8) will be included in this analysis. 

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These interim analyses are being conducted to explore the possibility that clinically meaningful 
effects may be observed early in the course of SRK-015 treatment. Based on the interim results, 
these insights may inform and expedite the planning of future clinical studies in SMA. 

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12. 
STUDY ADMINISTRATION 
The study administration structure is provided in Table 10. 
Table 10: 
Study Administrative Structure 
Sponsor Contact: 
Mara Sadanowicz 
Phone: +1.617.386.6842 
Email: msadanowicz@scholarrock.com 
Sponsor Medical Director: 
 
George Nomikos, MD, PhD 
Phone: +1.857.598.4874 
Email: gnomikos@scholarrock.com 
Medical Monitor: 
Nancy Campbell, MD 
Mobile phone: +1.513.978.2506 
Email: n.campbell@medpace.com 
Study Monitoring (US and EU): 
Medpace 
5375 Medpace Way 
Cincinnati, OH 45227 
Phone (Main): +1.513.579.9911 
Safety Laboratory (US and EU): 
Medpace Reference Laboratories 
5365 Medpace Way 
Cincinnati, OH 45227 
Phone (Main): +1.513.579.9911 
Central ECG Laboratory (US and EU): 
Medpace Core Laboratories 
5365 Medpace Way 
Cincinnati, OH 45227 
Phone (Main): +1.513.579.9911 
 

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13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
13.1. 
Study Monitoring 
This study will be performed in accordance with regulatory requirements outlined in Food and 
Drug Administration (FDA) 21 CFR Part 50, 21 CFR Part 54, 21 CFR Part 56, 21 CFR Part 312 
and 21 CFR Part 11, as well as the ICH GCP E6 Guidelines. A Study Monitor designated by the 
Sponsor will carefully monitor all aspects of the study for compliance with GCP, SOPs, and 
applicable government regulations. The Study Monitor will meet with the Investigator and staff 
shortly before the start of the study to review the procedures for study conduct and 
documentation. During the study, the Study Monitor will visit the site to verify record keeping 
and adherence to the protocol. 
The Investigator must prepare and maintain adequate and accurate records of all observations 
and other data pertinent to the clinical study for each study patient. Frequent communication 
between the clinical site and the Sponsor/designee is essential to ensure that the safety of the 
study is monitored adequately. The Investigator will make all appropriate safety assessments on 
an ongoing basis. The Sponsor’s medical representative may review safety information as it 
becomes available throughout the study. 
13.2. 
Audits and Inspections 
The Investigator should immediately notify the Sponsor representative of any announced or 
unannounced regulatory agency inspections. An auditing inspection may also be conducted by 
the Sponsor representative. 
The Investigator will allow Sponsor representatives, contract designees, authorized regulatory 
authority inspectors, and the IRB/IEC to have direct access to all documents pertaining to the 
study. 
13.3. 
Institutional Review Board/Independent Ethics Committee 
The Investigator must obtain IRB/IEC approval for the investigation. Initial IRB/IEC approval 
and all materials approved by the IRB/IEC for this study, including the patient consent form and 
recruitment materials, must be maintained by the Investigator and made available for inspection. 

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14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
An electronic data system will be used to ensure quality assurance and facilitate data capture 
during the study. The system is fully CFR 21 Part 11-compliant and provides for control and 
capture of study operations performance in real time. 
The Investigator or a qualified designee will prepare and maintain adequate and accurate study 
documents (medical records, ECGs, AE and concomitant medication reporting, raw data 
collection forms, etc.) designed to record all observations and other pertinent data for each 
patient receiving randomized study drug. The Investigator will ensure the accuracy, 
completeness, and timeliness of the data reported to the Sponsor and will cooperate with the 
Sponsor’s representative(s) for the periodic review of study documents to ensure the accuracy 
and completeness of the data capture system at each scheduled monitoring visit. Access to all 
source documentation will be made available for monitoring and audit purposes. Monitors will 
conduct 100% source document verification by comparing the eCRFs with the source documents 
to ensure consistency. Edit check programs, other forms of electronic validation, manual listings, 
and a query process will be executed to verify the accuracy of the database. The EDC system 
will maintain a full audit trail of electronic data changes. This information will be provided to the 
site by means of electronic or manual queries. Only enrolled patients will be entered into the 
database. 

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15. 
ETHICS 
15.1. 
Ethics Review 
The protocol and all protocol amendments must be signed and dated by the Investigator and 
approved in writing by the IRB/IEC in accordance with GCP prior to implementation. In 
addition, the IRB/IEC must approve the written informed consent and assent forms, any consent 
or assent form updates, patient recruitment procedures (e.g., advertisements), and any written 
information to be provided to patients prior to implementation. The Investigator must provide 
updates to the IRB/IEC with progress reports at appropriate intervals and a Study Progress 
Report following the completion, termination, or discontinuation of the Investigator’s 
participation in the study. 
15.2. 
Ethical Conduct of the Study 
The procedures set out in this clinical study protocol are designed to ensure that the Sponsor and 
the Investigator abide by the principles of the ICH guidelines on GCP and the Declaration of 
Helsinki (Version 2013). The clinical study will also be carried out in keeping with national and 
local legal requirements (in accordance with US Investigational New Drug regulations 
[21 CFR 56]). 
15.3. 
Written Informed Consent and Assent 
Written informed consent will be obtained from each patient if the patient is legally an adult. If 
the patient is legally a minor, informed consent document will be signed by the patient’s parent 
or legal guardian and patient’s oral or written assent obtained, if applicable and in accordance 
with regulatory and legal requirements of the participating location, before study procedures are 
conducted. As part of this procedure, the Investigator must explain orally and in writing, the 
nature, duration, and purpose of the study, and the action of the drug in such a manner that the 
patient and/or their parent or legal guardian is aware of the potential risks, inconveniences, or 
AEs that may occur. Patients and/or their parents or legal guardians should be informed that they 
are free to withdraw from the study at any time and that they will receive all information that is 
required by federal regulations and ICH guidelines. The Principal Investigator or a qualified 
designee will provide the Sponsor with a copy of the IRB/IEC-approved ICF prior to the start of 
the study. 
15.4. 
Patient Confidentiality 
The anonymity of participating patients must be maintained. Patients will be identified on study 
documents by their Patient number and birth date (if allowed based on local data protection 
regulations), not by name. Documents that identify the patient (e.g., the signed informed consent 
document) must be maintained in confidence by the Investigator. The Investigator agrees not to 
use or disclose protected health information other than as permitted or required by the patient 
authorization or as required by law. 

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16. 
DATA PROTECTION 
16.1. 
Organizational and Technical Arrangements to Avoid Unauthorized 
Access, Disclosure, Dissemination, Alteration, or Loss of Information 
and Personal Data Processed 
The conduct of this study and the processing of any personal data collected from each patient (or 
from a patient’s healthcare professional or other relevant third-party sources) by the Sponsor or 
designee, the site and the Investigator for use in the study will fully adhere to the requirements 
set out in applicable data protection and medical privacy laws or regulations, including, without 
limitation, the General Data Protection Regulation (GDPR) EU 2016/679. Sponsor or designee 
shall ensure that at all times it has an appropriate legal basis for processing personal data under 
applicable data protection law. Measures will be implemented in case of data security breach. 

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17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Inspection of Records 
Regulatory agencies may request access to all study records, including source documents, for 
inspection and copying, in keeping with country regulations. The Investigator will permit the 
designated Sponsor representatives and regulatory bodies to have direct access to the source 
documents to verify data represented in the eCRF. 
17.2. 
Retention of Records 
All source documents (e.g., ICFs, laboratory reports, imaging scans, progress notes, medical 
histories, physical and diagnostic findings, diagnosis and pharmacy records, and study drug 
dispensing/disposition records) that support data in the eCRFs of each study patient must be 
retained in the files of the responsible Investigator. 
According to ICH guidelines, essential documents should be retained for a minimum of 2 years 
after the last approval of a marketing application in an ICH region and until there are no pending 
or contemplated marketing applications in an ICH region, or if at least 2 years have elapsed since 
the formal discontinuation of clinical development of the investigational medicinal product. 
However, these documents should be retained for a longer period if required by the applicable 
legal requirements. 
If the responsible Investigator retires, relocates, or for any other reason withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The Sponsor representative must be notified in writing of the name and 
address of the new custodian, prior to the transfer. 

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18. 
PUBLICATION POLICY 
All information concerning SRK-015, including but not limited to, Sponsor operations, patent 
applications, formulas, manufacturing processes, scientific data, and formulation information, 
supplied to the Investigator by a Sponsor representative and not previously published, is 
considered confidential and remains the sole property of the Sponsor. The Investigator must 
agree to use this information solely for the purposes of carrying out this study and must not use it 
for other purposes without the Sponsor’s advanced written consent. 
The information developed in this study will be used by the Sponsor in connection with the 
continued development of SRK-015 and thus may be disclosed to other clinical Investigators or 
government regulatory agencies. The Investigator is obligated to provide the Sponsor with all 
data obtained in the study. 

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