Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Investor Presentation (January 2023)
77 slides from Scholar Rock's investor presentation, Jan 9, 2023
Slide 1: Deep Insights Advancing Impactful Medicines
Deep InsightsAdvancingImpactful Medicines January 2023
Slide 2: Disclaimers
Disclaimers Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock, Inc. (“Scholar Rock”), including without limitation, Scholar Rock’s expectations regarding its strategy, its product candidate selection and development timing, including timi
Slide 3: Transforming Patient Lives, Targeting High Unmet Medical Need
Scholar Rock: Transforming Patient Lives, Targeting High Unmet Medical Need 3 Global leader in TGFB superfamily biology Targeting the latent forms of growth factors Exquisite selectivity to deliver differentiated therapeutic profiles Revolutionary Platform Rich preclinical pipeline focused on high u
Slide 4: Revolutionary Approach to Regulating TGFβ Superfamily
Revolutionary Approach to Regulating TGFβ Superfamily Implicated in Devastating Diseases 4 Scholar Rock’s R&D Platform Transforming Medical Practice Selectively target the latent form of growth factors in the microenvironment of cells and tissues with uniquely designed antibodies Overcome the challe
Slide 5: Robust Pipeline of Novel Product Candidates
DISCOVERY/PRECLINICAL PHASE 1 PHASE 2 PHASE 3 2023 MILESTONES SPINAL MUSCULAR ATROPHYApitegromab (selective anti-latent myostatin) 36-month TOPAZ data SAPPHIRE: LPI IMMUNO-ONCOLOGYSRK-181 (Selective context-independent, anti-latent TGFβ-1) Rolling clinical data updates ANEMIASelective anti-RGMc IND-
Slide 6: Leadership Team: Experienced in Drug Development and Commercialization
Leadership Team: Experienced in Drug Development and Commercialization 6 Jay Backstrom, MD, MPH President & CEO 30 years of clinical R&D experience, leading multiple successful regulatory approvals Ted Myles, MBA Chief Operating Officer & CFO 25 years of progressive experience in clinical and commer
Slide 7: Apitegromab: The Next Potential Transformative Therapy for SMA
Apitegromab: The Next Potential Transformative Therapy for Patients with Spinal Muscular Atrophy (SMA)
Slide 8: Apitegromab: Potential Muscle-Directed Therapy for SMA
Apitegromab: Potential Muscle-Directed Therapy for SMA 8 * Based on Animal Model Data; 1. Adapted from: SMA Foundation Overview. http://www.smafoundation.org/wp-content/uploads/2012/03/SMA-Overview.pdf.; Accessed April 18, 2021; 2. Long KK, et al. Hum Mol Genet. 2019;28(7):1077-1088; 3. Pirruccello-
Slide 9: SMA disease burden and unmet need
9 *TOPAZ Phase 2 trial evaluated patients with Type 2 and 3 SMA (did not include Type 1) 1. Lally et al, Orphanet Journal of Rare Diseases, 2017; 2. SMA Europe. SMATracker. About SMA. Accessed January 24, 2022. https://smatracker.eu/what-is-spinal-muscular-atrophy; 3. National Organization for Rare
Slide 10: Opportunity for Muscle-Directed Therapy to Complement SMN-Directed Therapies
Patients continue to experience major functional impairments despite utilization of SMN-directed therapies Potential to Pioneer a New Treatment Era: Opportunity for Muscle-Directed Therapy to Complement SMN-Directed Therapies 10 PHASE 3 TRIAL DESIGN Type 1, 2 ,3 1 day -12 years of age (Non-ambulator
Slide 11: Apitegromab Offers Potential to Address Unmet Patient Need
Apitegromab Offers Potential to Address Unmet Patient Need 11 HFMSE=Hammersmith Functional Motor Scale-Expanded 1. Mercuri E et al.; N Engl J Med 2018; 378:625-635; DOI: 10.1056/NEJMoa1710504; cherish trial results. This third-party information is provided for background only and is not intended to
Slide 12: Phase 2 TOPAZ Trial: Safety and Efficacy Data
Phase 2 TOPAZ Trial: Safety and Efficacy Data from First Muscle-directed Treatment Candidate in SMA
Slide 13: TOPAZ Age 2-12 Analysis in Pooled Non-Ambulatory Cohorts
TOPAZ Age 2-12 Analysis* in Pooled Non-Ambulatory Cohorts (20mg/kg) Transformative Potential as Add-On for Apitegromab1,2 13 Mean HFMSE Increase OF 4.4 POINTS with majority experiencing ≥ 3-point increases on top of background SMN therapy HFMSE Gains Also Notable in subset of individuals in this ana
Slide 14: Sizable, Sustained Increases in HFMSE Observed Over 24 Months
Sizable, Sustained Increases in HFMSE Observed Over 24 Months of ApitegromabPooled Non-Ambulatory Patients Excluding Data Post Scoliosis Surgery (all dose groups) 14 For the 24-month evaluation, an observed case analysis was conducted, which pooled all the non-ambulatory patients (Cohorts 2 and 3) a
Slide 15: Continued Increase in RULM Observed at 24 Months
Continued Increase in RULM Observed at 24 Months of Apitegromab Pooled Non-Ambulatory Patients Excluding Data Post Scoliosis Surgery (all dose groups) 15 For the 24-month evaluation, an observed case analysis was conducted, which pooled all the non-ambulatory patients (Cohorts 2 and 3) and was based
Slide 16: No Serious Safety Risks Identified Over 24 Months
No Serious Safety Risks IdentifiedOver 24 Months of Apitegromab Treatment 16 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 17: SAPPHIRE Phase 3 Pivotal Trial
Sapphire Phase 3 Pivotal Trial
Slide 18: Ongoing SAPPHIRE Phase 3 Trial Overview
Ongoing SAPPHIRE Phase 3 Trial Overview 18 Randomized, double-blind, placebo-controlled, parallel arm design (n=204) Enrolling patients on SMN-directed therapy (nusinersen or risdiplam) Anticipate completing enrollment in 2023 TREATMENT (52 weeks) Apitegromab (20 mg/kg IV q4w) + SMN-directed therapy
Slide 19: Executing on the Promise: Apitegromab SMA Trials
2023 enrollment 2024 data 2025 launch Executing on the Promise: Apitegromab SMA Trials 19 WHERE WE WERE Phase 2 12-Month COMPLETE 24-Month EXTENSION COMPLETE WHERE WE AREPhase 3 WHERE WE PLAN TO GO 36-Month EXTENSION IN PROCESS 12-Month IN PROCESS Ambulatory patients Type 1 patients (including those
Slide 20: SRK-181: Potential Backbone for a New Era of Cancer Immunotherapy
SRK-181: Potential Transformative Backbone for a New Era ofCancer Immunotherapy
Slide 21: Resistance to Checkpoint Inhibitor Therapies Remains a Significant Clinical Challenge
Resistance to Checkpoint Inhibitor (CPI) Therapies Remains a Significant Clinical Challenge 21 1. Source: Gores, M. (2022). In the eye of the storm: PD-(L)1 inhibitors weathering turbulence [White paper]. IQVIA. https://www.iqvia.com/library/white-papers/in-the-eye-of-the-storm-pd-l-1-inhibitors-wea
Slide 22: Strong Scientific Rationale for TGFβ Inhibition in Immuno-Oncology
Strong Scientific Rationale for the Role of TGFβ Inhibition in Immuno-Oncology 22 “Bristol Myers Squibb Enters Agreement to Acquire Forbius TGF-beta Program” August 2022. “Merck to Acquire Tilos Therapeutics: Merck Gains Portfolio of Investigational Antibodies Modulating TGFβ” $773 million total pot
Slide 23: SRK-181: Unique Latent TGFβ-1 Selective Approach
SRK-181: Unique Latent TGFβ-1 Selective Approach to Overcoming Checkpoint Inhibitor Resistance 23 Traditional Target“Mature” growth factor 1. Wakefield LM, Winokur TS, Hollands RS, Christopherson K, Levinson AD, Sporn MB. Recombinant latent transforming growth factor beta 1 has a longer plasma half-
Slide 24: SRK-181 + Anti-PD1 Overcomes Immune Exclusion
SRK-181-mIgG1 + Anti-PD1 Overcomes Immune Exclusion 24 Anti-PD1/ SRK-181-mIgG1 Anti-PD1 Overcoming immune exclusion Tumor micro-environment Preclinical data published in Science Translational Medicine. Martin CJ, et al. Sci Transl Med. 2020 Mar 25;12(536):eaay8456. https://scholarrock.com/platform/p
Slide 25: DRAGON Phase 1 POC Trial Design
DRAGON Phase 1 POC Trial to Evaluate SRK-181’s Ability to Overcome Primary Resistance to Checkpoint Inhibitors 25 * A cohort of 2000 mg Q2W (n=3) was also evaluated. **The clear cell RCC cohort will also explore the effects of SRK-181 in patients with relapsed response after anti-PD-(L)1 treatment.
Slide 26: DRAGON Part A: Safety
DRAGON Part A: Safety 26 PART A1 Treatment-Emergent AEs Related to SRK-181, All Grades >10% PART A2 Treatment-Emergent AEs Related to SRK-181 or Anti-PD(L)1, All Grades >10% Dose (MG) 80N=1 240N=1 800N=3 1600N=4 2400N=3 3000N=3 2000N=4 AllN=19 Fatigue 0 1 0 0 1 0 1 3 (15.8%) Decreased Appetite 1 0 1
Slide 27: DRAGON Part A: Preliminary Efficacy Data
X X X X X X X X X X X X X X X X X X X Ovarian Ovarian Ovarian Pancreatic Pancreatic Colorectal Colorectal Colorectal Colorectal Colorectal Colorectal Testicular Prostate Prostate Prostate Prostate Primary Unknown Primary Unknown Head and Neck Months 0 1 2 3 4 5 6 7 8 9 10 11 12 X X X X X X X X X X X
Slide 28: Preliminary Efficacy in Combination with Pembrolizumab
Preliminary Efficacy Data in Combination with Pembrolizumab: Best Response in Target Lesions 28 Best Response in Target Lesions Best Response of PR Best Response of SD Best Response of PD Ongoing Percent Change from Baseline 800 mg q3w 800 mg q3w 1600 mg q3w 1600 mg q3w 1600 mg q3w 1600 mg q3w 2400
Slide 29: SRK-181: Encouraging Early Clinical Data Consistent with Hypothesis
SRK-181: Encouraging Early Clinical Data Consistent with Hypothesis 29 TGFβ pathway evaluation (PD) Target engagement (blood) TGFβ-1 signaling (tumor p-SMAD2 & RNAseq) Immunophenotyping, including immune exclusion status Tumor immune contexture (e.g., tumor CD8+ T cells) Immune cell contexture (tumo
Slide 30: SRK-181 summary: differentiation and clinical pathway
30 *(PD-1/PD-L1) First in class monoclonal antibody targeting latent and context-independent binding to TGFβ1 Differentiated from other TGFβ inhibitors by its novel selectivity Offers potential to avoid toxicity and dose-limiting challenges of non-selective TGFβ inhibition approaches Differentiation
Slide 31: Next Horizon: Fibrosis
Next Horizon: Fibrosis
Slide 32: TGFβ is Established as Key Driver of Fibrosis
TGFβ is Established as Key Driver of Fibrosis Across Multiple Diseases 32 Nature Reviews , April 25, 2016 NATURE REVIEWS | NEPHROLOGY TGF-β: the master regulator of fibrosis Xiao-ming Meng1, David J. Nikolic-Paterson2 and Hui Yao Lan3 Nature Reviews. August 19, 2014 NATURE REVIEWS | RHEUMATOLOGY Tra
Slide 33: Targeting Presenting Molecule/TGFβ-1 Complexes Provides Context Specificity
GARP Presents TGFβ on Tregs LRRC33 Presents TGFβ on Macrophages LTBP1 & 3 Present TGFβ in Connective Tissue Targeting Presenting Molecule/TGFβ-1 Complexes Provides Context Specificity Targeting Latent TGFβ-1 Complexes Creates Multiple “Handles” For Selectivity 33 Latent TGF-β GARP Treg Integrin expr
Slide 34: LTBP-49247 Reduces TGFβ Signaling and Fibrosis in Preclinical Models
LTBP-49247 Reduces TGFβ Signaling and Fibrosis in Preclinical Models of Kidney Fibrosis 34 LTBP-49247 reduces a TGFβ PD biomarker in kidneys of Col4a3 KO mice (Alport Syndrome model) LTBP-49247 reduces fibrosis in kidneys of Alport model ** p < 0.01 One way ANOVA vs. IgG HYP=hydroxyproline Efficacy
Slide 35: Opportunities Across Multiple Fibrotic Indications
Significant Opportunities to Address High Unmet Need Across Multiple Fibrotic Indications 35 Alport Syndrome (AS) Focal Segmental Glomerulosclerosis (FSGS) IgA Nephropathy (IgAN) Primary Sclerosing Cholangitis (PSC) Diffuse Cutaneous Systemic Sclerosis (dcSSc) Idiopathic Pulmonary Fibrosis (IPF) Col
Slide 36: Next Horizon: Iron-Restricted Anemia
Next Horizon: Iron-Restricted Anemia
Slide 37: BMP6/RGMc Pathway is a Validated Regulator of Iron Homeostasis
BMP6/RGMc Pathway is a Well Validated Regulator of Systemic Iron Homeostasis Fig: Muckenthaler, M.U., Rivella, S., Hentze, M.W. and Galy, B. (2017) A Red Carpet for Iron Metaboism. Cell, 168(3): 344-361 1: Kuns-Hashimoto R, et al. (2008) Selective binding of RGMc/hemojuvelin, a key protein in system
Slide 38: HJV-35202: High-Affinity Antibody Selective for HJV/RGMc
HJV-35202: A High-Affinity Antibody Demonstrating Selective Inhibition of HJV/RGMc and Robust PK/PD in Cynos 38 Potent in vitro binding affinity (KD=3.9E-11) Highly specific to RGMc/HJV with well understood mechanism Sustained PD effect in single dose Cyno study Specific to RGMc over other RGM famil
Slide 39: Opportunities to Target Iron-Restricted Anemias
Significant Opportunities to Target Iron-Restricted Anemias Across Multiple Indications 39 Chronic Kidney Disease (CKD) Anemia of Chronic Inflammation (AI) Myelofibrosis (MF) Targeting RGMc/HJV for anemia is well validated and relatively de-risked High levels of hepcidin, the main regulator of syste
Slide 40: Scholar Rock Summary
Scholar Rock Summary ss ScholarRock
Slide 41: Key Investment Highlights
41 Key Investment Highlights Revolutionary Platform Overcome the Challenges targeting the latent forms of growth factors Discover and Develop monoclonal antibodies with extraordinary selectivity Positioned For Success Upcoming Data Readouts for both clinical programs $205M financing in June 2022 Yea
Slide 42: Appendix
Appendix $$§ ScholarRock.
Slide 43: Motor Gains on SMN Therapies Appear to Plateau After Initial Gains
Plateau of HFMSE increases observed following initial treatment effect of risdiplam, although longer timeframes currently under investigation HFMSE=Hammersmith Functional Motor Scale-Expanded. Mercuri E, et al. Presented at: World Muscle Society Congress 2020, P. 257 Oskoui M, et al. Presented at: 2
Slide 44: Majority Started on SMN Therapy After Age 5 Do Not Experience Motor Increases
1. Mercuri E, et.al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378:625-635. 2. Efficacy and safety of risdiplam (RG7916) in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA) Roche/PTC Therapeutics This third-party information is
Slide 45: SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ
SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ 45 Largest HFMSE gains observed in the non-ambulatory Type 2/3 SMA cohorts Exploratory age 2-12 analysis in non-ambulatory Type 2/3 showed transformative potential HFMSE gains evident by 12 months of treatment Dose response seen (greater ef
Slide 46: TOPAZ Subject Disposition, Demographics and Baseline Characteristics
TOPAZ Subject Disposition, Demographics and Baseline Characteristics1,2 46 AMBULATORY PATIENTS NON-AMBULATORY PATIENTS COHORT 1 COHORT 2 COHORT 3 20 mg/kg monotherapy 20 mg/kg + nusinersen 20 mg/kg + nusinersen 2 mg/kg + nusinersen 20 mg/kg + nusinersen N (dosed) 11 12 15 10 10 Mean age at screening
Slide 47: Non-Ambulatory High Dose Cohort: Initiated Nusinersen Age <5
Non-Ambulatory Type 2 High Dose Cohort: Initiated nusinersen age <51,2 47 Sizable increases in HFMSE observed in patients already treated with chronic maintenance nusinersen Improved: 88% (7/8) ≥ 5-point increase: 63% (5/8) > 10-point increase: 38% (3/8) Continuous and durableimprovements observed t
Slide 48: Non-Ambulatory Type 2/3 Cohort: Initiated Nusinersen Age ≥5
Non-Ambulatory Type 2/3 Cohort: Initiated nusinersen age ≥51,2 48 Majority of patients improved in HFMSE (despite initiating background nusinersen age ≥ 5) ≥ 1-point increase: ~67% ≥ 3-point increase: ~30% Durability of effect observed through 12-months of treatment *Intent-to-treat analysis exclude
Slide 49: TOPAZ Topline 12-Month Data in Type 2/3 SMA
TOPAZ Topline 12-Month Data Showed Apitegromab’s Transformative Potential in Patients with Type 2/3 SMA 49 Crawford T et al. TOPAZ topline results; Presented at CureSMA, 2021 Virtual SMA Research & Clinical Care Meeting; June 9-11, 2021 * Pooled cohorts of non-ambulatory patients treated with apiteg
Slide 50: HFMSE Improvements Across Age Range of Non-Ambulatory Patients
*Pooled cohorts of non-ambulatory patients treated with apitegromab 20 mg/kg and 2 mg/kg; excludes 4 patients who each missed 3 doses of apitegromab due to COVID-19-related site access restrictions and were not included in the primary (intent-to-treat) analysis. Data on file. Scholar Rock, Inc. Camb
Slide 51: WHO Motor Development Milestone Achievements
WHO Motor Development Milestone Achievements Further Support Apitegromab’s Potential to Improve Motor Function1 51 Non-ambulatory Type 2/3 Patients # of patients gaining ≥ 1 WHO motor milestone(s) Pooled 7/35 Initiated nusinersen age < 5 4/20 Initiated nusinersen age ≥ 5 3/15 WHO motor milestone ana
Slide 52: Significance of HFMSE and RULM
Significance of Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) 52 HFMSE Assesses the physical abilities of patients with Types 2/3 SMA ABLE TO: Touch Head Above Ear Level whilst maintaining stable trunk and head Roll From Supine to Prone over the right side
Slide 53: TOPAZ Extension Period: 24-Month Patient Disposition
TOPAZ Extension Period: 24-Month Patient Disposition 53 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 0 1 Not Having Valid HFMSE testing at Month 24
Slide 54: Strong Evidence of Dose Response Observed Over 24 Months
SRK-015 20 mg/kg (N=10) SRK-015 2 mg/kg (N=10) Strong Evidence of Dose Response Observed Over 24 Months Further Supported by Data from Low Dose to High Dose Switch in Non-Ambulatory Patients 54 20 mg/kg throughout Switched from 2 mg/kg to 20 mg/kg Dose-switching period Crawford T et al. TOPAZ EXTENS
Slide 55: Reported Impact of Scoliosis Surgery on Motor Abilities in SMA
Reported Impact of Scoliosis Surgery on Motor Abilities in SMA 55 Dunaway Young et al. 2020 Scoliosis Surgery HFMSE Total Score 3-month post-surgery assessment 14/17 Lost >3 points on the HFMSE (mean change = - 12.1, SD = 8.9) Functionally meaningful change 13/17 Minimal HFMSE changes within ± 2 poi
Slide 56: Sizable, Sustained Increases in HFMSE Observed at 24 Months
Sizable, Sustained Increases in HFMSE Observed At 24 Months of ApitegromabPooled Non-Ambulatory Patients 56 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/kg and does not exclude any patients
Slide 57: Dose Response Supported by Low Dose to High Dose Switch
Strong Evidence of Dose Response Observed Over 24 MonthsFurther Supported by Data from Low Dose to High Dose Switch in Non-Ambulatory Patients 57 Most patients in Cohort 3 who switched from 2 mg/kg to 20 mg/kg continued to show HFMSE improvement Study Day Patient with scoliosis surgery Apitegromab i
Slide 58: Continued Increase in RULM Observed at 24 Months
Continued Increase in RULM Observed at 24 Months of Apitegromab Pooled Non-Ambulatory Patients 58 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/kg and does not exclude any patients who missed
Slide 59: Cohort 3: Mean RULM Score Change Over Time
Cohort 3: Mean RULM Score Change Over TimeRULM Trended Up in Low Dose Arm Patients After Switch to High Dose 59 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/kg and does not exclude any patie
Slide 60: Correlation of HFMSE to RULM Increased Over 24 Months
Correlation of HFMSE to RULM Increased Over 24 MonthsPooled Non-Ambulatory Patients 60 Crawford T et al. TOPAZ EXTENSION: 24-MONTH EFFICACY AND SAFETY OF APITEGROMAB IN PATIENTS WITH LATER-ONSET SPINAL MUSCULAR ATROPHY (TYPE 2 AND TYPE 3 SMA) Podium Presentation Presented at CureSMA; June 2022. This
Slide 61: PEDI-CAT, PROMIS and ESBBT Measures
PEDI-CAT: Measure of activities of daily living PROMIS (Fatigue): Measure of Patient Fatigue ESBBT (Fatigability): Measure of how fast a patient fatigues 1 2 3 PRO measurement tool4 Muscle endurance measurement tool6 4-point scale (1=unable to 4=easy) assessment of various activities, higher scores
Slide 62: Continuous Improvements in ADL and Fatigue Measures Over 24 Months
Non-Ambulatory Patients Showed Continuous Improvements in ADL and Fatigue Measures Over 24 Months of Apitegromab Treatment1,2 62 Tertiary Endpoints: Improvements in ADL and Fatigue Apitegromab treatment in non-ambulatory type 2 resulted in patients improving in patient-reported outcomes related to s
Slide 63: Stabilization or Improvements in ADL and Fatigue Measures over 24 Months
Apitegromab treatment in non-ambulatory types 2 and 3 resulted in patients improving in patient-reported outcomes related to self-sufficiency and fatigue Non-Ambulatory Patients Showed Stabilization or Improvements in ADL and Fatigue Measures over 24 Months of Apitegromab Treatment1,2 63 Tertiary En
Slide 64: Continued Improvement in Fatigability and Endurance Measures
Non-Ambulatory Patients Continued to Improve in Fatigability and Endurance Measures, Which May be Complementary to Upper Limb Function Improvements over 24 Months1 64 The ESBBT is the first validated and sensitive fatigability test for proximal arm function in SMA and may be complementary to outcome
Slide 65: Therapeutic Potential in Ambulatory Type 3 SMA Cohort at 24 Months
Therapeutic Potential of Apitegromab Observed in the Ambulatory Type 3 SMA Cohort at 24 Months1-4 65 Ambulatory Patients (Revised Hammersmith Scale; RHS) 24-Month Analysis COHORT 1 20 mg/kg pooled1 (n=21) 20 mg/kg Monotherapy4 (n=11) 20 mg/kg + nusinersen2,3 (n=10) Mean change from baseline, (95% CI
Slide 66: Serious Treatment-Emergent Adverse Events
Fourteen patients experienced a serious TEAE, all assessed by the respective trial investigator as unrelated to apitegromab: One patient treated with 2 mg/kg dose (Cohort 3) was hospitalized due to adenoidal hypertrophy and tonsillar hypertrophy to perform scheduled adenotonsillectomy (Grade 2). Eve
Slide 67: Non-Serious Grade 3 Events
Four patients presented with non-serious Grade 3 events, all assessed by the respective trial investigator as unrelated to apitegromab: One patient treated with 20 mg/kg dose (Cohort 1) presented with post lumbar puncture syndrome. Event resolved without sequelae. One patient treated with 20 mg/kg d
Slide 68: SRK-181: Backbone For Next Era of Cancer Therapy
SRK-181: Transformative Potential as the Backbone For Next Era of Cancer Therapy 68 CPI Combination (solid tumors) Other Combinations (solid tumors) & Hematologic Other immunotherapies Chemotherapy XRT Otherapplications Myelofibrosis Liquid tumors 1st line immunotherapy First in class monoclonal ant
Slide 69: SRK-181 Inhibits Latent TGFβ-1 Across All Compartments of the Tumor
Regulatory T cell Tumor Associated Macrophage Cancer Associated Fibroblasts (Stromal cells) Tumor cells SRK-181 Targets latent TGFβ-1 Inhibits activation of latent TGFβ-1 across ALL compartments Turns it off at the source Context-Independent: SRK-181 Inhibits Latent TGFβ-1 Across All Compartments of
Slide 70: SRK-181 Therapeutic Hypothesis: Advantages of Latent TGFβ-1 Inhibitor
SRK-181 Therapeutic Hypothesis: Potential Advantages of Latent TGFβ-1 Inhibitor 70 SRK-181* Bifunctional TGFβ/CPI ALK5 Inhibitor Nonselective TGFβ antibody Selectivity for TGFβ-1: potential for wider therapeutic window and improved safety Ability to combine with any anti-PD-(L)1 Ability to optimize
Slide 71: TGFβ-1 Blockade Rendered Preclinical Tumor Models Susceptible to Anti-PD1
TGFβ-1 Blockade with SRK-181-mIgG1 Rendered Preclinical Tumor Models Susceptible to Anti-PD1 Therapy 71 Days after treatment initiation Tumor volume (mm3) Anti-PD1/ SRK-181-mIgG1(3 mg/kg QW) 4/14 Anti-PD1/ SRK-181-mIgG1(10 mg/kg QW) 8/14 Preclinical data published in Science Translational Medicine.
Slide 72: Combination Treatment Led to Melanoma Tumor Regression and Survival Benefit
SRK-181-mIgG1 Combination Treatment Led to Melanoma Tumor Regression and Survival Benefit 72 *P<0.01. †P<0.05 Log-rank (Mantel-Cox test) vs anti-PD1. * * † Days after treatment initiation Tumor Regression Survival Benefit Anti-PD1 + SRK-181-mlgG1 (30 mg/Kg/wk) Anti-PD1 + SRK-181-mlgG1 (3 mg/Kg/wk) A
Slide 73: Selectivity of SRK-181 Offers Potential to Overcome Toxicity Challenges
Selectivity of SRK-181 Offers Potential to Overcome Toxicity and Dose-limiting Challenges of Non-selective TGFβ Pathway Approaches 73 Preclinical data published in Science Translational Medicine. Martin CJ, et al. Sci Transl Med 2020 Mar 25;12(536): eaay8456. *Source: Anderton MJ, et al. Induction o
Slide 74: TGFβ-1 Implicated as Driving Primary Resistance to Checkpoint Inhibitors
Bladder urothelial carcinoma Had & neck squamous carcinoma Kidney clear cell carcinoma Kidney papillary cell carcinoma Liver hepatocellular carcinoma Lung adenocarcinoma Skin cutaneous melanoma Stomach adenocarcinoma Acute myeloid leukemia Adrenocortical cancer Brain lower grade glioma Breast invasi
Slide 75: Biomarker Strategies Employed in DRAGON Trial
Biomarker Strategies Employed in DRAGON Trial 75 Multiple tissue-based and circulating biomarker analyses to be evaluated in DRAGON study Higher resolution histochemical characterization of tumor immune contexture (e.g. CD8+) Classification of inflamed, excluded or immune desert tumors and tumor nes
Slide 76: Clear Evidence of Target Engagement: Circulatory TGFβ-1
Clear Evidence of Target EngagementPharmacodynamic Biomarker Results for Part A: Circulatory TGFβ-1 76 Yap T et al. SRK-181, a latent TGFβ1 inhibitor: safety, efficacy, and biomarker results from the dose escalation portion of a phase I trial (DRAGON trial) in patients with advanced solid tumors (Po
Slide 77: Preclinical Rationale to Evaluate Peripheral Samples for SRK-181 Activity
Preclinical Data Provide Scientific Rationale to Evaluate Peripheral Samples for Evidence of SRK-181 Activity 77 MBT-2 bladder tumor model IgG, anti-PD-1 and SRK-181-mIgG1 dosed d1, d7 Analysis on day 10 Circulating MDSC Levels Correlate with Tumor Volume Both tumoral and circulatory MDSC are being
Scholar Rock Holding — Investor Presentation (January 2023) on 6ix