8-K
Scholar Rock Holding Corp (SRRK)
8-K
2025-01-14
For: 2025-01-14
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event Reported): January 14, 2025
Scholar Rock Holding Corporation
(Exact Name of Registrant as Specified in Charter)
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| Delaware | **** | 001-38501 | **** | 82-3750435 |
| (State or Other Jurisdiction of<br>Incorporation) | | (Commission File Number) | | (I.R.S. Employer Identification Number) |
301 Binney Street , 3rd Floor , Cambridge , MA **** 02142
(Address of Principal Executive Offices) (Zip Code)
( 857 ) 259-3860
(Registrant’s telephone number, including area code)
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
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| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered |
|---|---|---|
| Common Stock, par value $0.001 per share | SRRK | The Nasdaq Global Select Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2). Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01. Regulation FD Disclosure.
A copy of the presentation that will be used by management of Scholar Rock Holding Corporation at the 43rd Annual J.P. Morgan Healthcare Conference on January 14, 2025 is being furnished as Exhibit 99.1 to this report on Form 8-K.
The information in this Item 7.01 and Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section. It may only be incorporated by reference in another filing under the Exchange Act or the Securities Act of 1933, as amended, if such subsequent filing specifically references the information furnished pursuant to Item 7.01 and Exhibit 99.1 of this Current Report on Form 8-K.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
| Exhibit<br><br>No. | Description | ||
|---|---|---|---|
| 99.1 | | Scholar Rock Holding Corporation Corporate Presentation dated January 14, 2025. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | ||
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Scholar Rock Holding Corporation | ||
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| Date: January 14, 2025 | By: | /s/ Junlin Ho |
| Junlin Ho | ||
| General Counsel & Corporate Secretary |
| © 2025 Scholar Rock, Inc. All rights reserved.<br>43rd Annual<br>J.P. Morgan<br>Healthcare Conference<br>Jay Backstrom, M.D., MPH<br>President and Chief Executive Officer<br>January 14, 2025<br>1<br>Exhibit 99.1 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Forward-Looking Statements<br>Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock Holding Corporation and Scholar Rock, Inc. (collectively,<br>“Scholar Rock”), including without limitation, Scholar Rock’s expectations regarding its strategy, its product candidate selection and development timing, including timing for the<br>initiation of and reporting results from its preclinical studies and clinical trials for apitegromab, SRK-439, linavonkibart and other product candidates and indication selection and<br>development timing, its cash runway, the ability of any product candidate to perform in humans in a manner consistent with earlier nonclinical, preclinical or clinical trial data, and<br>the potential of its product candidates and proprietary platform. The use of words such as “may,” “could,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,”<br>“estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward-looking statements for the purposes of the<br>safe harbor provisions under The Private Securities Litigation Reform Act of 1995. All such forward-looking statements are based on management's current expectations of<br>future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such<br>forward-looking statements. These risks and uncertainties include, without limitation, that preclinical and clinical data, including the results from the Phase 3 trial of apitegromab<br>or Part A or Part B of the Phase 1 trial of linavonkibart, are not predictive of, may be inconsistent with, or more favorable than, data generated from future or ongoing clinical<br>trials of the same product candidate; Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on<br>the expected timeline; the data generated from Scholar Rock’s nonclinical and preclinical studies and clinical trials, including from the EMBRAZE clinical trial; information provided<br>or decisions made by regulatory authorities; competition from third parties that are developing products for similar uses; Scholar Rock’s ability to obtain, maintain and protect<br>its intellectual property; the success of Scholar Rock’s current and potential future collaborations; Scholar Rock’s dependence on third parties for development and manufacture<br>of product candidates including, without limitation, to supply any clinical trials; Scholar Rock’s ability to manage expenses and to obtain additional funding when needed to<br>support its business activities; its ability to establish or maintain strategic business alliances; its ability to receive priority or expedited regulatory review or to obtain regulatory<br>approval of apitegromab; its ability to expand globally and the anticipated commercial launch in the United States of apitegromab in the fourth quarter of 2025; as well as those<br>risks more fully discussed in the section entitled "Risk Factors" in Scholar Rock’s Form 10-K for the year ended December 31, 2023, and Quarterly Report on Form 10-Q for the<br>quarter ended September 30, 2024, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock’s subsequent filings with the Securities<br>and Exchange Commission. Any forward-looking statements represent Scholar Rock’s views only as of today and should not be relied upon as representing its views as of any<br>subsequent date. All information in this press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law.<br>This presentation may also contain estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our<br>industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions,<br>and estimates of our future performance and the future performance of the markets in which we compete are necessarily subject to a high degree of uncertainty and risk.<br>Apitegromab and SRK-181 are investigational drug candidates under evaluation. Apitegromab, linavonkibart, SRK-256, SRK-373, and SRK-439 have not been approved for any<br>use by the FDA or any other regulatory agency and the safety and efficacy of apitegromab, linavonkibart, SRK-256, SRK-373, and SRK-439 have not been established.<br>2 |
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| OUR MISSION<br>To discover, develop, and deliver life-changing<br>therapies by harnessing cutting-edge science<br>to create new possibilities for people living with<br>serious diseases<br>Industry-leading technology,<br>life-changing potential<br>3 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>TODAY’S FOCUS<br>Scholar Rock is Moving with a Sense of Urgency<br>To Bring Transformative Medicines to Patients<br>4<br>*Pending regulatory approval.<br>EXPAND<br>Apitegromab Development<br>Program: Building a Pipeline<br>in a Product<br>COMMERCIALIZE<br>Execute a Successful<br>Commercial Launch*<br>ADVANCE<br>Anti-myostatin Program<br>into Cardiometabolic<br>Indications<br>1 2 3<br>Building off<br>successful Phase 3<br>SAPPHIRE results<br>$2B+ Opportunity in SMA<br>BLA and MAA 1Q 2025<br>submission on track Pursuing<br>opportunities<br>for apitegromab in additional<br>rare neuromuscular diseases<br>2Q 2025 EMBRAZE<br>Phase 2 study results<br>expected<br>IND submission on track<br>for 3Q 2025 for SRK-439,<br>a highly innovative myostatin<br>inhibitor<br>Initiate earlier<br>treatment<br>with OPAL study for patients<br>under 2 years of age with SMA |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Scholar Rock’s Target<br>Latent Growth Factor Traditional Target<br>“Mature” Active Growth Factor<br>5<br>Scholar Rock Has Succeeded Where Others Have Failed<br>Selectivity Drives Success<br>Targeting the ‘cage’ before<br>growth factor is released allows<br>for exquisite selectivity<br>Challenging to target because of<br>high homology across super-family<br>RIGHT<br>TIME<br>Latent<br>Form<br>RIGHT<br>TARGET<br>Validated<br>Biology |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>6<br>Growing Pipeline Across High Value Therapeutic Areas<br>Industry-leading Anti-myostatin Programs<br>*undisclosed indication<br>**UC=urothelial cell carcinoma; RCC=renal cell carcinoma.<br>THERAPEUTIC AREA<br>PRODUCT<br>(target)<br>Discovery/<br>Preclinical PHASE 1 PHASE 2 PHASE 3 Commercial<br>NEUROMUSCULAR<br>Apitegromab<br>(latent myostatin)<br>(undisclosed)<br>CARDIOMETABOLIC<br>Apitegromab<br>(latent myostatin)<br>SRK-439<br>(novel latent myostatin)<br>IMMUNO-ONCOLOGY<br>Linavonkibart (SRK-181)<br>(latent TGFβ1)<br>HEMATOLOGY SRK-256<br>(RGMc)<br>FIBROSIS SRK-373<br>(LTBP1/3)<br>Our Differentiated Approach: Target Latent Growth Factor<br>*Indication<br>OBESITY<br>ANEMIA<br>Fibrotic indications<br>UC, ccRCC**<br>OBESITY<br>SPINAL MUSCULAR ATROPHY |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Transforming the<br>Treatment of SMA<br>Commercializing Apitegromab<br>7 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>8<br>Progressive Muscle Weakness Remains Core Unmet Need in SMA<br>1. Finkel RS et al. “Final Safety and Efficacy Data From the SHINE Study in Participants With Infantile-Onset and Later-Onset SMA.” Presented at Cure SMA Annual Conference, July 2024.<br>2. Cure SMA State of SMA Annual Report. Published May 6, 2024; Cure SMA. Education on adult patient expectations according to copy number and disease status at time of report. September<br>2022.; Internal Scholar Rock market research.<br>This information from third-party studies is provided for background purposes only and is not intended to convey or imply a comparison to the SAPPHIRE clinical trial results.<br>HFMSE=Hammersmith Functional Motor Scale Expanded; SMA=Spinal Muscular Atrophy.<br>What do patients seek<br>most from a new<br>treatment in SMA?2<br>97% said<br>Improvement in muscle strength<br>90% said<br>Achieving new motor function<br>88% said<br>Stabilizing motor function<br>Motor Function Over Time of Patients Treated with Nusinersen1 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>SELECTIVITY DRIVES SUCCESS<br>The Only Muscle-Targeted Therapy with Clinical Success in SMA<br>9<br>* Based on apitegromab combined dose (10 mg/kg and 20 mg/kg) + SOC versus placebo + SOC (Hochberg multiplicity adjustment).<br>† 12.5% of patients on placebo + SOC achieved a ≥3-point improvement in HFMSE<br> SOC=Standard of care (i.e., nusinersen or risdiplam); HFMSE=Hammersmith Functional Motor Scale–Expanded.<br>CONSISTENT<br>clinically meaningful<br>benefit observed<br>across<br>all age groups<br>(2-21)<br>FAVORABLE<br>SAFETY<br>profile consistent with<br>>48 months experience<br>in Phase 2 TOPAZ trial<br>30%<br>of apitegromab patients<br>ACHIEVED ≥3<br>POINT IMPROVEMENT IN<br>HFMSE†<br>1.8<br>POINT<br>IMPROVEMENT<br>(p=0.0192)<br>in HFMSE* vs. placebo<br>Positive Phase 3 Trial Using Gold Standard SMA Scale<br>SUCCESSFUL PIVOTAL TRIAL<br>On Track to Submit BLA and MAA in 1Q 2025 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Apitegromab: Potential to Transform the Standard of Care in SMA<br>Finkel RS et al. “Final Safety and Efficacy Data From the SHINE Study in Participants With Infantile-Onset and Later-Onset SMA.” Presented at Cure SMA Annual Conference, July 2024<br>*Patient age based on those received active treatment (mean or median)<br>1. This information from third-party studies is provided for background purposes only and is not intended to convey or imply a comparison to the SAPPHIRE clinical trial results.<br>CI=Confidence Interval; EXP=Exploration Subpopulation; HFMSE=Hammersmith Functional Motor Scale Expanded; LS=Least Squares; MEP=Main Efficacy Population; SOC=standard of care.<br>• Despite effective SMN-targeted therapy, long-term trajectory of SMA patients remains that of progressive decline in motor function<br>• Treatment with apitegromab has improved motor function vs. placebo<br>KEY<br>TAKEAWAYS<br>Motor Function Over Time of Patients Treated with Nusinersen<br>Placebo + SOC n= 50 50 50 48 50 49 48<br>Apitegromab + SOC n= 106 105 105 101 102 102 102<br>Motor Function Over Time of Patients in SAPPHIRE<br>10 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>11<br>Apitegromab: Shifting the Treatment Paradigm in SMA<br>Transformative Therapeutic Potential<br>• Validated with a rigorous approach:<br>Strong trial design using a gold-standard SMA scale<br>• Potential to transform standard of care in SMA<br>Suitable for a Broad SMA Population<br>• Consistency of effect seen across age groups studied<br>• Long-term tolerability shown to date<br>Long-Term Treatment Experience<br>• >4 years treatment in SMA in Phase 2 TOPAZ trial<br>• >90% retention in TOPAZ<br>• 98% continuation from SAPPHIRE to ONYX long-term extension |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>12<br>Expanding our Impact: Initiating Phase 2 OPAL Trial in mid-2025<br>Studying apitegromab in patients under 2 years old<br>Potential to alter the course of<br>SMA in a broad population<br>CHANGING<br>More Lives<br>Reaching patients earlier in their<br>treatment journey<br>TIME<br>Is Muscle<br>Including patients who received<br>gene therapy<br>EXPANDING<br>Our Impact |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Scholar Rock is Positioned for a Successful Commercial Launch<br>THE RIGHT...<br>Potential to alter<br>the course of SMA<br>MEDICINE<br>Clear unmet need and first<br>and only muscle-targeted<br>therapy<br>MARKET<br>Engagement, patient<br>focus & execution<br>PLAN<br>13 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>14<br>Existing Therapies Generate ~$4.5B in Annual Revenues<br>Addressing the Motor Neuron<br>1. Hua Y, et al. Nature. 2011;478(7367):123-6.<br>2. Figure adapted from: SMA Foundation Overview. http://www.smafoundation.org/wp-content/uploads/2012/03/SMA-Overview.pdf.; Accessed April 18, 2021.<br>SMA=Spinal muscular atrophy; SMN=Survival motor neuron.<br>...but do not directly address<br>muscle atrophy<br>SMN therapies<br>slow further degeneration of<br>motor neurons1<br>Motor neuron<br>degeneration2<br>Muscle fiber<br>atrophy<br>There is further potential to<br>regain vital muscle function by also<br>addressing the progressive muscle<br>atrophy and associated weakness in SMA<br>Currently no<br>approved<br>muscle-targeted<br>therapy |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>$2B+ Global Opportunity for Apitegromab in SMA<br>~$4.5B1<br>Global revenue for<br>three SMN-targeted<br>therapies<br>Apitegromab global<br>revenue potential<br>>$2.0B2<br><br>Apitegromab global<br>revenue potential<br>$2B+2<br><br>1st<br>And only<br>muscle-targeted<br>treatment to<br>show clinical<br>benefit in SMA<br>SMA patients are diagnosed, treated, and still need more to continue to improve their lives<br>15<br>1 Revenue as of Biogen 4Q23 financial update, Roche 4Q23 financial update, and Novartis 4Q23 financial update.<br>2 Scholar Rock internal estimates as of December 2024.<br>SMA=Spinal muscular atrophy; SMN=Survival motor neuron. |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>SMA is a Defined Market and Optimal For Apitegromab Launch<br>Patients are diagnosed and treated, but still need more<br>Patients Identified<br>and Treated<br>~25K patients in US and EU<br>100% US newborn<br>screening<br>2/3 of US patients on<br>treatment<br>Patient, HCP, and<br>payers recognize remaining<br>need to improve function<br>1.<br>Clear Unmet<br>Need<br>2.<br>Organized community<br>aligned on need for muscle<br>targeted therapy<br>Engaged Patient<br>Community<br>3.<br>Established value for<br>improving function<br>Payer<br>Receptivity<br>4.<br>The SMA community is calling for new treatments to improve function<br>16 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>17<br>Advantaged by Deep Rare Disease Commercial Experience<br>Commercial, medical, and<br>advocacy teams with<br>deep rare disease<br>launch experience<br>Launches<br>Leadership<br>Seasoned executive<br>team with average of<br>20+ years industry<br>experience |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Partnering With the SMA Community and Engaging Top HCPs<br>© 2024 Scholar Rock, Inc. All rights reserved.<br>Disease<br>EDUCATION<br>Amplifying the patient voice<br>in first muscle-focused SMA<br>disease education campaign<br>Partnering with US and<br>European patient advocacy<br>groups<br>Patient<br>ADVOCACY<br>Adults and Children Children Only Adults Only<br>Engaging with 100%<br>of Cure SMA-identified centers<br>HCP<br>ENGAGEMENT<br>18 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Preparing for a Successful Launch<br>Delivering Apitegromab Customer Engagement<br>Commercial launch supply secured<br>Rare disease distribution partners selected<br>Home infusion at launch<br>Account team with average 30 years experience<br>engaging with US commercial and federal payers<br>Efficient US customer-facing footprint of<br>~50 FTEs planned<br>Establishing European presence<br>19 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>SMA is Only the Beginning: Creating Possibilities with<br>Apitegromab in Additional Neuromuscular Diseases<br>*Numbers represent prevalence in the US and Europe based on internal market research.<br>SM=Spinal Muscular Atrophy; ALS=Amyotrophic Lateral Sclerosis; DMD=Duchenne Muscular Dystrophy; BMD=Becker’s Muscular Dystrophy; FSHD=Facioscapulohumeral muscular dystrophy.<br>Building a neuromuscular franchise is a key driver towards future growth<br>20<br>Opportunities<br>to impact<br>more patients<br>SMA ~25k<br>DMD and BMD ~38k ~12k<br>FSHD ~40k<br>ALS ~69k |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Apitegromab is the Foundation of a Future Multi-Billion Dollar<br>Neuromuscular Franchise*<br>*Subject to regulatory approval.<br>Commercial<br>Launch*<br>Global expansion,<br>starting with Europe<br>SMA expansion with Ph 2 OPAL<br>trial for patients under 2 and<br>subcutaneous formulation<br>Neuromuscular expansion of<br>apitegromab into additional<br>indications<br>Unlocking value<br>in our pipeline<br>by targeting various aspects<br>of neuromuscular diseases<br>to help people living with<br>rare, devastating diseases<br>21 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Unlocking Value in<br>Our Anti-Myostatin<br>Platform<br>Cardiometabolic Program Update<br>22 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>GLP-1 RAs are Transforming Weight Loss for Millions of People<br>Source: UBS Bank, GLP-1: A medication worth $126 billion in sales by 2029? https://www.ubs.com/global/en/investment-bank/insights-and-data/2024/glp-1-a-medication.html.<br>GLP-1 RA=GLP-1 receptor agonist.<br>Recently approved<br>GLP-1 RAs are<br>highly effective<br>in weight loss &<br>experiencing<br>rapid uptake<br>BY<br>2029...<br>40 million people on GLP-1 RAs<br>$126 billion in Sales*<br>23 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>However, Patients Want Healthier Weight Loss*<br>*Source: Scholar Rock market research, completed December 2024.<br>GLP-1 RA=GLP-1 receptor agonist.<br>WEAKNESS<br>is a Concern<br>Patients complain of<br>reduced strength<br>after GLP-1 RA<br>treatment<br>Patients hope for a<br>combination treatment<br>approach to address<br>this need<br>Improved<br>LEAN MASS<br>Significant<br>Weight REGAIN<br>in 40-100% of patients<br>after stopping GLP-1 RA<br>treatment<br>Scholar Rock’s unique highly selective approach to targeting latent myostatin<br>has the potential to address these patient needs<br>Patients feel good about the number<br>on the scale, but there are issues with<br>muscle loss … they complain of<br>weakness or reduced strength.<br>Obesity Clinician<br>24 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>25<br>Industry-Leading Anti-Myostatin Platform:<br>Leveraging Apitegromab’s Success to Advance the Obesity Program<br>*Expected timelines<br>POC=Proof of Concept; GLP-1 RA=GLP-1 receptor agonist.<br>POC data<br>readout Q2*<br>Ph 2 proof-of-concept trial<br>APITEGROMAB + tirzepatide<br>2025<br>IND*<br>SRK-439 + GLP-1 RA<br>Novel asset<br>for cardiometabolic<br>indication Phase 1 trial<br>Cardiometabolic<br>Disorders<br>• EMBRAZE POC readout<br>in Q2 2025<br>• SRK-439 IND<br>submission in Q3 2025<br>Testing hypothesis<br>of selective anti-myostatin antibody<br>in obese population |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>26<br>GLP-1 RA=GLP-1 receptor agonist.<br>Preclinical data to date show strong potential<br>to support healthier weight loss in combination<br>with GLP-1 RAs:<br>SRK-439: Potential Best in Class<br>Strong Scientific<br>Validation and Promising<br>Preclinical Evidence<br>Preservation of lean mass<br>Improvement in metabolic parameters<br>Increase in lean mass and attenuation of fat<br>mass regain following GLP-1 RA withdrawal<br>Greater potency compared to an<br>anti-ACTRII antibody<br>Works across the class of GLP-1 RAs |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>SRK-439 Protects from Tirzepatide-Induced Muscle Loss in DIO Mice<br>qNMR % Lean Mass Change from Baseline Key Observations<br>• Considerable lean mass loss with<br>tirzepatide treatment<br>• Combination with SRK-439 led to dose-dependent lean mass preservation<br>• Lean mass preservation seen with doses<br>as low as 0.3 mg/kg and lean mass gain at<br>higher doses<br>• Dose dependent enhancement of fat mass<br>loss also observed, improving overall body<br>composition<br>DIO=Diet-induced obesity.<br>27<br>One Way ANOVA<br>* p < 0.05<br>** p < 0.01<br>*** p < 0.001<br>**** p < 0.0001 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Signaling receptor shared by<br>Myostatin, GDF-11 & Activin A<br>28<br>Potential to Optimize Benefit-Risk with Myostatin Selectivity<br>Promyostatin Pro-GDF-11 Proactivin<br>GDF-11 Activin A<br>ActRIIA/B<br>Apitegromab<br>SRK-439 Other Approaches<br>• GI problems, e.g., diarrhea, pancreatitis3-6<br>• Nose bleeds (epistaxis), low platelet count,<br>telangiectasias7-10<br>• Reduction in reproductive hormones in<br>males and females3, 7, 11, 12<br>• Acne, rash, skin abscesses5, 13, 14<br>• Madarosis (loss of eyebrows or eyelashes)14<br>Favorable<br>safety<br>profile 1,2<br>Health Risks Observed with<br>Non-Selective Inhibition of ActRII Pathway:<br>Myostatin<br>1. Barrett et al. Adv Therapy. 2021; 2. Crawford T et al. Neurology. 2024; 3. Garito T et al. Clin Endocrinol (Oxf). 2018; 4. Amato AA et al. Neurology. 2021; 5. Heymsfield SB et al. JAMA. 2021;<br>6. Vanhoutte F et al. J Clin Pharmacol. 2020; 7. Attie KM et al. Muscle Nerve. 2013; 8. Attie KM et al. Am J Hematol. 2014; 9. Campbell C et al. Muscle Nerve. 2017; 10. Hoeper MM et al. N Engl J Med. 2023;<br>11. Ruckle J et al. J Bone Miner Res. 2009; 12. Sherman ML et al. J Clin Pharmacol. 2013; 13. Muntoni F et al. Neurol Ther. 2024. 14. Di Rocco M et al. Nat Med. 2023. |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>29<br>Data from Phase 2 Proof-of-Concept Study of Apitegromab in<br>Obesity Expected Q2 2025<br>*Due to expedited enrollment and timing of semaglutide clinical supply, all enrolled patients received tirzepatide.<br>Apitegromab dose regimen will be 10 mg/kg Q4W, based on projected exposure in the obese population comparable to that of 20 mg/kg Q4W in SMA.<br>Tirzepatide and semaglutide dose regimen will follow the United States Prescribing Information.<br>Randomized, double-blind, placebo-controlled (n=102 enrolled)<br>Enrolled patients who are overweight or obese<br>Enrollment completed ahead of schedule; topline data expected in Q2 2025<br>Screening (Up to 4 weeks)<br>• Male or female, age ≥18 and ≤65 years old at the<br>time of informed consent<br>• Stable body weight within 90 days of screening<br>• BMI ≥30.0 kg/m2 to ≤45.0 kg/m2 or ≥27.0 kg/m2<br>to <30.0 kg/m2 with the presence of 1 or more<br>weight-related comorbid condition(s)<br>ENDPOINTS<br>Primary Endpoint (Week 24)<br>Change from baseline in lean mass by DEXA scan<br>Secondary Endpoints<br>Additional weight loss measures, safety & tolerability, PK/PD<br>Treatment (24 weeks)<br>Apitegromab Q4W + tirzepatide or semaglutide* QW<br>Placebo Q4W + tirzepatide or semaglutide* QW<br>ADDITIONAL<br>Exploratory Endpoints (Week 24 and 32)<br>Cardiometabolic profile (e.g., HbA1c), body<br>composition, physical function<br>R<br>N=50<br>N=50<br>8 weeks<br>(24 weeks)<br>Primary endpoint<br>(32 weeks)<br>Exploratory endpoints |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Goals of the EMBRAZE Proof-of-Concept Study<br>Initiated trial in May 2024,<br>ahead of target timeline<br>Enrollment completed in<br>September 2024<br>Topline data expected in<br>Q2 2025<br>30<br>INSIGHTS GAINED<br>FROM EMBRAZE STUDY<br>to inform SRK-439<br>development<br>Study Aims to Demonstrate<br>Preservation of lean mass in obese<br>or overweight patients<br>Safety and tolerability<br>Potential to improve metabolic profile<br>and physical function |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Tirzepatide-Induced Weight Loss Accompanies Significant<br>Muscle Loss<br>Figure from Jastreboff, A.M. et al. N Engl J Med. 2022;387(3):205-216.<br>* Data from Phase 3 clinical trial of tirzepatide in adults with obesity.<br>Tirzepatide<br>DECREASE<br>in lean mass of<br>10.9%<br>accompanies<br>DECREASE<br>in body weight<br>Percent Change in Body Weight -24<br>-20<br>-16<br>-12<br>-8<br>-4<br>0<br>-3.1<br>-15.0<br>-19.5<br>-20.9<br>0 4 8 12 16 20 24 36 48 60 72 TRE<br>Weeks Since Randomization<br>-2.4<br>-16.0<br>-21.4<br>-22.5<br>Tirzepatide, 5 mg Tirzepatide, 10 mg Tirzepatide, 15 mg Placebo<br>Percent Change in Body Weight by Week (efficacy estimand)<br>Time period of EMBRAZE Overall mean baseline weight = 104.8 kg<br>31 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Conclusion<br>32 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>33<br>Delivering on the Mission of Bringing Transformative<br>Medicines to Patients<br>* Pending approval from regulatory agencies.<br>Apitegromab is an investigational drug candidate under evaluation and has not been approved by any regulatory agency.<br>Leveraging R&D success to build a multi-billion dollar biopharmaceutical company<br>COMMERCIALIZE<br>Successful<br>commercial launch*<br>Setting the stage for<br>a multi-billion dollar<br>opportunity<br>EXPAND<br>Expanding<br>neuromuscular<br>franchise<br>Advancing anti-myostatin program<br>in obesity<br>Advancing the pipeline<br>INNOVATE<br>Developed platform<br>based on selective<br>targeting of latent<br>growth factors<br>Advanced industry-leading antibody<br>design & protein<br>engineering<br>DEVELOP<br>Successfully executed<br>positive Phase 3 trial<br>in SMA |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>2025 Milestones: A Transformative Year for Scholar Rock<br>34 * Pending regulatory approval.<br>Apitegromab is an investigational drug candidate under evaluation and has not been approved by any regulatory agency.<br>• Submit FDA and EMA<br>applications in 1Q 2025<br>• US launch expected in<br>4Q 2025 and EU launch<br>to follow*<br>• SMA: Under 2 study<br>initiation planned<br>for mid-2025<br>• Exploring additional<br>neuromuscular<br>indications<br>• Obesity: EMBRAZE<br>readout expected in<br>2Q 2025<br>• SRK-439 IND filing<br>planned for 3Q 2025<br>EXPAND<br>Apitegromab Development<br>Program: Building a Pipeline<br>in a Product<br>COMMERCIALIZE<br>Apitegromab in<br>SMA<br>ADVANCE<br>Anti-myostatin Program<br>into Cardiometabolic<br>Indications<br>1 2 3 |
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| © 2025 Scholar Rock, Inc. All rights reserved.<br>Thank you!<br>35 |
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