Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Corporate Update (June 2022)
36 slides from Scholar Rock's corporate update, Jun 17, 2022
Slide 1: Apitegromab Update
Confidential and Proprietary Apitegromab Update Data extracted April 7, 2022 Anti - Myostatin Antibody With Transformative Potential in Patients with Type 2 and Type 3 SMA
Slide 2: Disclaimers
Disclaimers Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock, Inc. (“Schol ar Rock”), including without limitation, Scholar Rock’s expectations regarding its strategy, its product candidate selection and development timing, inclu din g t
Slide 3: Agenda
Agenda 3 SMA Disease Background & Current Treatment Landscape Apitegromab TOPAZ Extension Period: 24 - Month Data Apitegromab SAPPHIRE Phase 3 Trial Overview Business Update
Slide 4: Revolutionary Approach to Regulating Highly Sought-After Growth Factors
4 Revolutionary Approach to Regulating Highly Sought - After Growth Factors Implicated in Devastating Diseases Scholar Rock’s Target Growth Factor Precursor (Latent Form) Scholar Rock’s R&D Platform Transform Medical Practice • Pursue important targets with well - validated biology but are difficult
Slide 5: Apitegromab Shows Transformative Potential in Patients with Type 2 and 3 SMA
Apitegromab Shows Transformative Potential in Patients with Type 2 and 3 SMA • Spinal Muscular Atrophy (SMA) remains a devastating and debilitating disease despite the utilization of SMN therapies • Motor neuron defect with loss of muscle mass • Current therapies target motor neuron deterioration; m
Slide 6: Spinal Muscular Atrophy Overview
6 Spinal Muscular Atrophy Overview Type 1 14% Type 2 51% Type 3 35% Global disease with 30,000 - 35,000 affected in U.S. and Europe alone 1,2.3 TOPAZ* 12 - month results showed transformative potential in non - ambulatory Types 2 and 3 patients Represents ~2/3 of overall patient population Motor neu
Slide 7: Patients with Types 2 and 3 SMA Continue to Experience Major Functional Deficits
Patients with Types 2 and 3 SMA Continue to Experience Major Functional Deficits Despite Improvement from Nusinersen 7 HFMSE=Hammersmith Functional Motor Scale - Expanded Darras, B., et.al. Nusinersen in later - onset spinal muscular atrophy. Neurology. May 2019; 92 (21) e2492 - e2506. This third -
Slide 8: Plateauing of HFMSE increases observed for nusinersen
HFMSE=Hammersmith Functional Motor Scale - Expanded. 1. Mercuri E, et al. Presented at: World Muscle Society Congress 2020, P. 257 2. Oskoui M, et al. Presented at: 2021 Muscular Dystrophy Association Clinical & Scientific Conference; March 15 - 18, 2021. Poster 80. This third - party information is
Slide 9: Summary of TOPAZ Extension Period: 24-Month Data
Summary of TOPAZ Extension Period: 24 - Month Data Sustained Benefit and Evidence of Continued Improvement □ Non - Ambulatory Types 2/3 SMA • Motor function associated with activities of daily living improved with apitegromab + nusinersen at 24 months: o Sizable and sustained gains in HFMSE scores o
Slide 10: Phase 2 TOPAZ Trial Design
Phase 2 Trial Design Apitegromab = nonproprietary name for SRK - 015 HFMSE=Hammersmith Functional Motor Scale Expanded; RHS=Revised Hammersmith Scale Data on file. Scholar Rock, Inc. Cambridge, MA Ambulatory Patients (Revised Hammersmith Scale) Non - Ambulatory Patients (Hammersmith Functional Motor
Slide 11: TOPAZ Subject Disposition, Demographics and Baseline Characteristics
Apitegromab is an investigational product candidate being evaluated for the treatment of spinal muscular atrophy. Apitegromab ha s not been approved by any regulatory authority and its safety and efficacy have not been established. © Scholar Rock, Inc. All rights r ese rved. April 2022 TOPAZ Subject
Slide 12: Extension Period Overview
Extension Period Overview 12 month 57 of 58 patients completed primary treatment period and enrolled in second year of therapy • 55 of 57 patients completed • High dose (20 mg/kg) patients stayed on high dose • Low dose (2 mg/kg) patients switched to high dose (20 mg/kg)* • Four patients had scolios
Slide 13: Significance of Hammersmith Functional Motor Scale Expanded (HFMSE)
Significance of Hammersmith Functional Motor Scale Expanded (HFMSE) Validated measure assessing the physical abilities of patients with Types 2/3 SMA o Consists of 33 items graded on a scale of 0 to 2: 0 denotes unable; 1 denotes performed with modification or adaptation; and 2 denotes without modif
Slide 14: Sizable, Sustained Increases in HFMSE Observed at 24 Months
Sizable, Sustained Increases in HFMSE Observed At 24 Months of Apitegromab Pooled Non - Ambulatory Patients Data on File. Scholar Rock, Inc. Cambridge, MA . Observed Case Analysis is based upon data available for a given timepoint, and this analysis population includes patients treated with th e low
Slide 15: Reported Impact of Scoliosis Surgery on Motor Abilities in SMA
Reported Impact of Scoliosis Surgery on Motor Abilities in SMA o The vast majority of patients in this peer - reviewed study lost >3 pts on the HFMSE as assessed at least 3 months post - surgery o 14/17 participants lost >3 points (mean change = - 12.1, SD = 8.9) on the HFMSE, representing a functio
Slide 16: Sizable, Sustained HFMSE Increases Excluding Data Post Scoliosis Surgery
Sizable, Sustained Increases in HFMSE Observed At 24 Months of Apitegromab Pooled Non - Ambulatory Patients Excluding Data Post Scoliosis Surgery Data on File. Scholar Rock, Inc. Cambridge, MA. 16 6 months 12 months 24 months 6 months 12 months 24 months Baseline Baseline Age 2 - 12 3.6 (1.2, 6.0) n
Slide 17: Strong Evidence of Dose Response Observed Over 24 Months
Strong Evidence of Dose Response Observed Over 24 Months Further Supported by Data from Low Dose to High Dose Switch 20 mg/kg throughout Switched from 2 mg/kg to 20 mg/kg Dose - switching period This analysis excludes from the Observed Case Analysis the HFMSE data attained post - scoliosis surgery d
Slide 18: PK and PD Data Consistent With Clinically Observed Dose Response
0 2 8 5 6 8 4 1 1 2 1 4 0 1 6 8 1 9 6 2 2 4 2 5 2 2 8 0 3 0 8 3 3 6 3 6 4 3 9 2 4 2 0 4 4 8 4 7 6 5 0 4 5 3 2 5 6 0 5 8 8 6 1 6 6 4 4 6 7 2 7 0 0 7 2 8 1 10 100 1000 10000 Time (days) M e a n ( ± S D ) L a t e n t M y o s t a t i n C o n c e n t r a t i o n ( n g / m L ) TOPAZ Cohort 1 (20 mg/kg) TO
Slide 19: Significance of the Revised Upper Limb Module (RULM)
Significance of the Revised Upper Limb Module (RULM) Evaluates Motor Performance in Upper Limbs o Evaluated upper limb tasks correspond to ability to perform everyday activities o Exc ept for 1 activity with a binary score, the items are scored 0 to 2: 0 denotes unable; 1 denotes able with modificat
Slide 20: Continued Increase in RULM Observed at 24 Months
Continued Increase in RULM Observed at 24 Months of Apitegromab Pooled Non - Ambulatory Patients Data on File. Scholar Rock, Inc. Cambridge, MA. Observed Case Analysis is based upon data available for a given timepoint, and this analysis population includes patients treated with the lower dose 2 mg/
Slide 21: Continued Increase in RULM Excluding Data Post Scoliosis Surgery
Continued Increase in RULM Observed at 24 Months of Apitegromab Pooled Non - Ambulatory Patients Excluding Data Post Scoliosis Surgery Data on File. Scholar Rock, Inc. Cambridge, MA. This analysis excludes data from 3 non - ambulatory patients after their scoliosis surgery during TOPAZ from the Obse
Slide 22: Correlation of HFMSE to RULM Increased Over 24 Months
Correlation of HFMSE to RULM Increased Over 24 Months Pooled Non - Ambulatory Patients -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 1011 1213 14 1516 1718 19 20 HFMSE Change from Baseline at EXT14/Day 728 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 R U L M C h a n g e f r o m B a s e l i n e a t E X T 1 4 / D a
Slide 23: Therapeutic Potential Observed in Ambulatory Type 3 SMA Cohort at 24 Months
Therapeutic Potential of Apitegromab Observed in the Ambulatory Type 3 SMA Cohort at 24 Months Ambulatory Patients (Revised Hammersmith Scale; RHS) 24 Month Analysis Cohort 1 20 mg/kg pooled (n=21) 20 mg/kg monotherapy (n=11) 20 mg/kg + nusinersen (n=10) Mean change from baseline (95% CI) - 1.8 ( -
Slide 24: No Serious Safety Risks Identified Over 24 Months of Apitegromab Treatment
No Serious Safety Risks Identified Over 24 Months of Apitegromab Treatment Treatment - Emergent Adverse Events (TEAEs)* 2 mg/kg dose (N=10) n (%) 20 mg/kg dose (N=48) n (%) Total (N=58) n (%) Any TEAE 10 (100) 45 (93.8) 55 (94.8) Any Serious TEAE 3 (30) 11 (22.9) 14 (24.1) Any TEAE leading to study
Slide 25: Summary of TOPAZ Extension Period: 24-Month Data
Summary of TOPAZ Extension Period: 24 - Month Data Sustained Benefit and Evidence of Continued Improvement □ Non - Ambulatory Types 2/3 SMA • Motor function associated with activities of daily living improved with apitegromab + nusinersen at 24 months: o Sizable and sustained gains in HFMSE scores o
Slide 26: Ongoing SAPPHIRE Phase 3 Trial Overview
Ongoing SAPPHIRE Phase 3 Trial Overview • Randomized, double - blind, placebo - controlled, parallel arm design • Enrolling patients on SMN therapy (nusinersen or risdiplam ) • Primary efficacy endpoint: mean HFMSE change from baseline at 12 months • Study start - up activities commenced Apitegromab
Slide 27: SAPPHIRE Details
SAPPHIRE Details Main population Endpoints Analysis Additional Data Opportunities • Primary efficacy: HFMSE • Additional efficacy measures: RULM, WHO, other outcome measures • Safety, PK/PD, ADA • Topline readout based of main efficacy population (age 2 - 12) is apitegromab 20 mg/kg* vs. placebo • I
Slide 28: Focused Pipeline of Novel Product Candidates
Focused Pipeline of Novel Product Candidates 28 Discovery - stage pipeline focused on the selective modulation of growth factor signaling APITEGROMAB SRK - 181 A selective inhibitor of myostatin activation being developed as the potential first muscle - directed therapy for the treatment of spinal m
Slide 29: Key Investment Highlights
Key Investment Highlights 29 • Designed to discover and develop monoclonal antibodies that can modulate growth factors with extraordinary selectivity • Designed to overcome the challenges that have plagued traditional approaches by targeting the precursor or latent forms of growth factors • Apitegro
Slide 30: Appendix
30 Appendix
Slide 31: Strong Evidence of Dose Response Observed Over 24 Months
Strong Evidence of Dose Response Observed Over 24 Months Further Supported by Data from Low Dose to High Dose Switch 31 Most patients in Cohort 3 who switched from 2 mg/kg to 20 mg/kg continued to show HFMSE improvement Study day is relative to the date of the first dose of 20 mg/kg Study Day Patien
Slide 32: Cohort 3: Mean RULM Score Change Over Time
Cohort 3: Mean RULM Score Change Over Time RULM trended up in low dose arm patients after switch to high dose All patients in Cohort 3 switched from 2 mg/kg to 20 mg/kg 1 of 9 patients in Cohort 3 switched from 2 mg/kg to 20 mg/kg 9 of 10 patients in Cohort 3 switched from to 2 mg/kg to 20 mg/kg Fig
Slide 33: Cohort 3 Patient Conversion Timeline to 20 mg/kg
4 of 10 patients in Cohort 3 switched from 2 mg/kg to 20 mg/kg 9 of 10 patients in Cohort 3 switched from 2 mg/kg to 20 mg/kg All patients in Cohort 3 switched from 2 mg/kg to 20 mg/kg Cohort 3 2 mg/kg Timing Patient Conversion Timeline to 20 mg/kg: • Day 560: 105 - 304, 110 - 301, 110 - 302, and 11
Slide 34: TOPAZ Extension Period: 24-Month Patient Disposition
TOPAZ Extension Period: 24 - Month Patient Disposition 34 Cohort 1 Ambulatory Non – Ambulatory Cohort 2 Cohort 3 Total # Non - Ambulatory Patients (2 - 21) 15 20 35 # Non - Ambulatory Patients (2 - 12) 9 20 29 Dropped Out (0 - 12 M) 1 0 0 0 Dropped Out (12 - 24 M) 1 1 1 Not Having Valid HFMSE testin
Slide 35: Overall Safety and Tolerability Profile: Serious TEAEs
Overall Safety and Tolerability Profile Over 24 Months of Treatment: Serious TEAEs 35 • Fourteen patients experienced a serious TEAE, all assessed by the respective trial investigator as unrelated to apitegromab : o One patient treated with 2 mg/kg dose (Cohort 3) was hospitalized due to adenoidal h
Slide 36: Overall Safety and Tolerability Profile: Non-Serious Grade 3 Events
Overall Safety and Tolerability Profile Over 24 Months of Treatment: Non - Serious Grade 3 Events 36 • Four patients presented with non - serious Grade 3 events, all assessed by the respective trial investigator as unrelated to apitegromab : o One patient treated with 20 mg/kg dose (Cohort 1) presen