Scholar Rock Holding Corporation · NASDAQ:SRRK
Scholar Rock — Investor Presentation (June 2023)
76 slides from Scholar Rock's investor presentation, Jun 30, 2023
Slide 1: Deep Insights Advancing Impactful Medicines Company Overview
Deep InsightsAdvancingImpactful Medicines Company Overview | June 2023
Slide 2: Forward-Looking Statements
© Scholar Rock, Inc. All rights reserved. 2023. Forward-Looking Statements 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 pro
Slide 3: Scholar Rock: Transforming Patient Lives, Addressing High Unmet Medical Need
Scholar Rock: Transforming Patient Lives, Addressing High Unmet Medical Need 3 Global leader in TGFβ superfamily biology Targeting the latent forms of growth factors Exquisite selectivity to deliver differentiated therapies Revolutionary Platform Rich preclinical pipeline focused on high unmet patie
Slide 4: Revolutionary Approach to Regulating TGFβ Superfamily Implicated in Devastating Diseases
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 ANTICIPATED 2023 MILESTONES SPINAL MUSCULAR ATROPHYApitegromab (selective anti- pro and latent myostatin) 36-month TOPAZ data SAPPHIRE: last patient enrolled expected in Q3 IMMUNO-ONCOLOGYSRK-181 (selective context-independent, anti-latent TGFβ-1) Rollin
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 Patients with SMA
Apitegromab: The Next Potential Transformative Therapy for Patients with Spinal Muscular Atrophy (SMA)
Slide 8: Apitegromab: Transformative Potential to Change the Standard of Care
Apitegromab: Transformative Potential to Change the Standard of Care 8 Apitegromab is an investigational drug candidate being evaluated for the treatment of spinal muscular atrophy (SMA). Apitegromab has not been approved for any use by the FDA or any other regulatory agency, and its safety and effi
Slide 9: Progressive Muscle Atrophy and Weakness in SMA
There is further potential to regain vital muscle function by also addressing the progressive muscle atrophy and associated weakness of SMA SMN therapies slow further degeneration of motor neurons1 Hallmarks of SMAProgressive Motor Neuron Loss and Muscle Atrophy Leading to Progressive Muscle Weaknes
Slide 10: SMA Patient Population by Type
10 *TOPAZ Phase 2 trial evaluated patients with Type 2 and 3 SMA (did not include Type 1) ** 2/3 of overall patient population has type 2 or 3 SMA, including ambulatory and nonambulatory patients. Percentages reflected here do not add up to 100% because the prevalences of Types 0, 4, and unknown are
Slide 11: Motor Function With SMN Therapies as Assessed by HFMSE
Motor Function With SMN Therapies as Assessed by HFMSE HFMSE appears to Plateau After Initial Gains 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.
Slide 12: Improving and Sustaining Muscle Function Remains an Unmet Need
Patients and caregivers want new therapies to address the following unmet needs2* : Improving and Sustaining Muscle Function Remains an Unmet Need 12 HFMSE=Hammersmith Functional Motor Scale-Expanded *Percentages represent percent of patients who named these unmet needs when asked “What are your mos
Slide 13: Apitegromab Offers Significant Potential to Address Unmet Needs
Apitegromab Offers Significant Potential to Address Unmet Needs 13 * Based on Animal Model Data; 1. Long KK, et al. Hum Mol Genet. 2019;28(7):1077-1088; 2. Pirruccello-Straub M, et al. Sci Reports. 2018;8(1):2292. doi:10.1038/s41598-018-20524-9 3. Figure adapted from: SMA Foundation Overview. http:/
Slide 14: Phase 2 TOPAZ Trial: Safety and Efficacy Data
Phase 2 TOPAZ Trial: Safety and Efficacy Data from First Muscle-Targeted Treatment Candidate in SMA
Slide 15: Phase 2 Trial Design
Phase 2 Trial Design1,2 15 Ambulatory Patients (Revised Hammersmith Scale) Safety RHS mean change from baseline at 12 months Ages 5-21 Type 3 SMA Open-label, single-arm Apitegromab 20 mg/kg IV q4w Receiving nusinersen Apitegromab monotherapy Nonambulatory Patients (Hammersmith Functional Motor Scale
Slide 16: Motor Function Outcomes by HFMSE Over 36 Months
Motor Function Outcomes by HFMSE Over 36 Months Improvements Were Substantial and Sustained 16 For the 36-month evaluation, an observed case analysis was conducted, which pooled all the nonambulatory patients (Cohorts 2 and 3) and was based upon the available data for given timepoints. This analysis
Slide 17: Motor Function Outcomes by RULM Over 36 Months
Motor Function Outcomes by RULM Over 36 Months Improvements Were Substantial and Sustained 17 For the 36-month evaluation, an observed case analysis was conducted, which pooled all the nonambulatory patients (Cohorts 2 and 3) and was based upon the available data for given timepoints. This analysis
Slide 18: Improvements in PRO Measures Consistent with Motor Function
Time (weeks) No. of observations Time (weeks) No. of observations Year 3 Year 2 Year 1 Pooled Nonambulatory Patients | Age 2 – 21 | All Doses | Over 36 Months Improvements in PRO Measures Were Consistent with Motor Function IMPROVEMENT PEDI-CAT Daily Activities IMPROVEMENT IMPROVEMENT N = 35; Baseli
Slide 19: New WHO Development Milestones Achieved Over 36 Months
Pooled Nonambulatory Patients New WHO Development Milestones Achieved Over 36 Months 19 Proportion of patients gaining new milestones in TOPAZ Cohort 2: BL (0%),12m (20%), 24m (7%), 36m (0%) Cohort 3 (all doses): BL (0%,) 12m (24%), 24m (26%), 36m (30%) Cohort 3: Randomized to 20mg/kg dose: 12m (25%
Slide 20: TOPAZ Safety Summary
TOPAZ Safety Summary Over 36 Months 20 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) 46 (95.8) 56 (96.6) Any serious TEAE 5 (50) 16 (33.3) 21 (36.2) Any TEAE leading to study drug discontinuation 0 1 (2.1) 1 (1.7)
Slide 21: Summary of TOPAZ Data
Summary of TOPAZ Data Substantial and Sustained Improvement Over 36 MONTHS 21 PRO=Patient Reported Outcome Data to date has shown substantial clinical benefit that is dose-dependent TOPAZ data suggest that apitegromab has the potential to transform care in SMA by directly addressing progressive musc
Slide 22: SAPPHIRE Phase 3 Pivotal Trial
Sapphire Phase 3 Pivotal Trial
Slide 23: SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ
SAPPHIRE Phase 3 Design is Optimized by Insights from TOPAZ 23 Substantial HFMSE gains observed in the nonambulatory Type 2/3 SMA cohorts Exploratory age 2-12 analysis in nonambulatory Type 2/3 showed transformative potential HFMSE gains substantial by 12 months of treatment Dose response seen (grea
Slide 24: Ongoing SAPPHIRE Phase 3 Trial Overview
Ongoing SAPPHIRE Phase 3 Trial Overview 24 Randomized, double-blind, placebo-controlled, parallel arm design (n=204) Enrolling patients who are on SMN-directed therapy (nusinersen or risdiplam) Anticipate completing enrollment in 3Q 2023 TREATMENT (52 weeks) Apitegromab (20 mg/kg IV q4w) + SMN-direc
Slide 25: Executing on the Promise: Apitegromab SMA Trials
Executing on the Promise: Apitegromab SMA Trials 25 SMA=Spinal Muscular Atrophy *Subject to regulatory approval WHERE WE AREPhase 3 12-Month IN PROCESS Long-term EXTENSION 3Q 2023 enrollment 2024 data 2025 launch* ANTICIPATED MILESTONES WHERE WE WERE Phase 2 12-Month COMPLETE 24-Month EXTENSION COMP
Slide 26: Apitegromab Summary: Potential First Muscle-Targeted Therapy in SMA
26 Potential first muscle-targeted therapy in SMA Robust body of data supports therapeutic potential Differentiation Strong pre-clinical evidence indicates upstream targeting of structurally differentiated latent myostatin avoids undesirable off-target effects Phase 2 TOPAZ trial demonstrated the th
Slide 27: SRK-181: Potential Backbone for a New Era of Cancer Immunotherapy
SRK-181: Potential Transformative Backbone for a New Era ofCancer Immunotherapy
Slide 28: Resistance to Checkpoint Inhibitor Therapies Remains a Significant Clinical Challenge
Resistance to Checkpoint Inhibitor (CPI) Therapies Remains a Significant Clinical Challenge 28 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 29: Strong Scientific Rationale for TGFβ Inhibition in Immuno-Oncology
Strong Scientific Rationale for the Role of TGFβ Inhibition in Immuno-Oncology 29 “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 30: SRK-181: Unique Latent TGFβ-1 Selective Approach
SRK-181: Unique Latent TGFβ-1 Selective Approach Designedto Overcome Checkpoint Inhibitor Resistance 30 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
Slide 31: SRK-181-mIgG1 + Anti-PD1 Overcomes Immune Exclusion
SRK-181-mIgG1 + Anti-PD1 Overcomes Immune Exclusion 31 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 32: DRAGON Phase 1 POC Trial Design
DRAGON Phase 1 POC Trial to Evaluate SRK-181’s Ability to Overcome Primary Resistance to Checkpoint Inhibitors 32 * A cohort of 2000 mg Q2W (n=3) was also evaluated. **The clear cell RCC and HNSCC cohorts will also explore the effects of SRK-181 in patients with relapsed response after anti-PD-1 tre
Slide 33: DRAGON Part A: Safety
DRAGON Part A: Safety PART A1 Monotherapy Treatment-Emergent AEs Related to SRK-181, All Grades >10% PART A2 Combination Treatment 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 (
Slide 34: DRAGON Part A: Preliminary Efficacy Data
Duration of Treatment DRAGON Part A: Preliminary Efficacy Data* 34 Part A1 (n=19) Part A2 (n=15) 8 patients had a best response of stable disease (SD) All 3 patients with ovarian cancer were stable for 6-10 months Yap T et al. Safety and Efficacy Results of SRK-181, a latent TGFβ1 inhibitor, from a
Slide 35: Preliminary Efficacy in Combination with Pembrolizumab
Preliminary Efficacy Data in Combination with Pembrolizumab: Best Response in Target Lesions 35 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 36: Summary of ccRCC Patients on Combination Treatment
36 Summary of ccRCC Patients on Combination Treatment (Part A2 and Part B) 11 ccRCC patients enrolled n=2 in Part A2 (all discontinued from study) and n=9 in Part B (5 pts remain on study) enrollment in Part B continues 3 confirmed PRs observed in ccRCC patients Patients are anti-PD-1 resistant pati
Slide 37: Summary of ccRCC Patients with PR in DRAGON
Summary of ccRCC Patients with PR in Dragon (Part A2 and Part B, Combination Treatment) Responded Pts SRK-181 Dose (mg, Q3W) Age (Year)/ Gender Lines of Prior Therapy IMDC Score at Screening Metastatic Sites at Screening Pt Status Duration of Treatment (wks) Best % Change in SOD* from Baseline Pt #1
Slide 38: SRK-181: Encouraging Early Clinical Data Consistent with Hypothesis
SRK-181: Encouraging Early Clinical Data Consistent with Hypothesis 38 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 39: SRK-181 Summary
39 *(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 40: Next Horizon: Fibrosis
Next Horizon: Fibrosis
Slide 41: TGFβ is Established as Key Driver of Fibrosis
TGFβ is Established as Key Driver of Fibrosis Across Multiple Diseases 41 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 42: Targeting Latent TGFβ-1 Complexes Creates Multiple Handles for Selectivity
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 42 Latent TGF-β GARP Treg Integrin expr
Slide 43: LTBP-49247 Reduced TGFβ Signaling and Fibrosis in Preclinical Models
LTBP-49247 Reduced TGFβ Signaling and Fibrosis in Preclinical Models of Kidney Fibrosis 43 LTBP-49247 reduced a TGFβ PD biomarker in kidneys of Col4a3 KO mice (Alport Syndrome model) LTBP-49247 reduced fibrosis in kidneys of Alport model ** p < 0.01 One way ANOVA vs. IgG HYP=hydroxyproline Efficacy
Slide 44: Opportunities Across Multiple Fibrotic Indications
Significant Opportunities to Address High Unmet Need Across Multiple Fibrotic Indications 44 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 45: Next Horizon: Iron-Restricted Anemia
Next Horizon: Iron-Restricted Anemia
Slide 46: BMP6/RGMc Pathway is a Well Validated Regulator of Systemic Iron Homeostasis
BMP6/RGMc Pathway is a Well Validated Regulator of Systemic Iron Homeostasis 46 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 sys
Slide 47: HJV-35202: High-Affinity Antibody Selectively Inhibiting HJV/RGMc
HJV-35202: An Investigational High-Affinity Antibody Demonstrating Selective Inhibition of HJV/RGMc and Robust PK/PD in Cynos 47 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 ove
Slide 48: Opportunities to Target Iron-Restricted Anemias
Significant Opportunities to Target Iron-Restricted Anemias Across Multiple Indications 48 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 49: Summary
Scholar Rock Summary ss ScholarRock
Slide 50: Key Investment Highlights
50 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 Cas
Slide 51: Appendix
Appendix $$§ ScholarRock.
Slide 52: TOPAZ Baseline Characteristics
TOPAZ Baseline Characteristics1,2 52 *Patients on average received ~2 years of nusinersen treatment at baseline and ~3 years of nusinersen treatment by the end of the TOPAZ study (12-months). SMN2 copy numbers were not available for all patients. †12-month baseline characteristics recorded in the ta
Slide 53: TOPAZ Patient Disposition
TOPAZ Patient Disposition Over 36 Months a. Patients stratified based on previous treatment with approved SMN therapy. b. Patients randomized to receive 2 or 20 mg/kg apitegromab. *Includes patients who crossed over from 2 mg/kg to 20mg/kg starting week 68 through week 104 ** Excludes patients on mo
Slide 54: Improvements in PRO Measures Consistent With Motor Function (Age 2-12)
Time (weeks) No. of observations Year 3 Year 2 Year 1 Year 3 Year 2 Year 1 PROMIS Fatigue (Proxy) Year 2 Year 3 Year 1 Year 2 Year 3 Year 1 Pooled Nonambulatory Patients | Age 2 – 12 | All Doses | Over 36 MonthsImprovements in PRO Measures Consistent With Motor Function 54 Time (weeks) No. of observ
Slide 55: PEDI-CAT Daily Activities Over 36 Months
PEDI-CAT Daily Activities Over 36 Months Improvements Were Substantial and Sustained 55 For the 36-month evaluation, an observed case analysis was conducted, which pooled all the nonambulatory patients (Cohorts 2 and 3) and was based upon the available data for given timepoints. This analysis popula
Slide 56: PEDI-CAT Daily Activities Over 36 Months
PEDI-CAT Daily Activities Over 36 Months Improvements Were Substantial and Sustained 56 For the 36-month evaluation, an observed case analysis was conducted, which pooled all the nonambulatory patients (Cohorts 2 and 3) and was based upon the available data for given timepoints. This analysis popula
Slide 57: PROMIS Fatigue (Proxy) Over 36 Months
PROMIS Fatigue (Proxy) Over 36 Months Improvements Were Substantial and Sustained 57 For the 36-month evaluation, an observed case analysis was conducted, which pooled all the nonambulatory patients (Cohorts 2 and 3) and was based upon the available data for given timepoints. This analysis populatio
Slide 58: TOPAZ Topline 12-Month Data
TOPAZ Topline 12-Month Data Showed Apitegromab’s Transformative Potential in Patients with Type 2/3 SMA 58 Crawford T et al. TOPAZ topline results; Presented at CureSMA, 2021 Virtual SMA Research & Clinical Care Meeting; June 9-11, 2021 * Pooled cohorts of nonambulatory patients treated with apitegr
Slide 59: TOPAZ Age 2-12 Analysis at 12 Months
TOPAZ Age 2-12 Analysis* in Pooled Nonambulatory Cohorts (20mg/kg) at 12 Months Mean Increase of Motor Function Outcomes by HFMSE was Significant 59 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
Slide 60: TOPAZ 12-Month Data: Nonambulatory Type 2 High Dose Cohort
TOPAZ 12-Month Data | Nonambulatory Type 2 High Dose CohortInitiated nusinersen age <51,2 60 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
Slide 61: TOPAZ 12-Month Data: Nonambulatory Type 2/3 Cohort
TOPAZ 12-Month Data | Nonambulatory Type 2/3 CohortInitiated nusinersen age ≥51,2 61 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-tre
Slide 62: TOPAZ 12-Month HFMSE Changes and Duration of Prior Nusinersen
TOPAZ 12-Month HFMSE Changes and Duration of Prior Nusinersen 62 Patients enrolled were already in the chronic maintenance phase of nusinersen Lack of clear correlation between 12-month HFMSE & duration of prior nusinersen exposure in patients aged 2 – 21 suggests motor function improvement mainly a
Slide 63: Majority of Patients Started on SMN Therapy After Age 5 Do Not Experience Motor Function 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 64: Significance of HFMSE and RULM
Significance of Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) 64 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 65: 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 66: Reported Impact of Scoliosis Surgery on Motor Abilities in SMA
Reported Impact of Scoliosis Surgery on Motor Abilities in SMA 66 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 67: SRK-181: Backbone for Next Era of Cancer Therapy
SRK-181: Transformative Potential as the Backbone For Next Era of Cancer Therapy 67 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 68: SRK-181 Designed to Inhibit Latent TGFβ-1 Across All Compartments
Regulatory T cell Tumor Associated Macrophage Cancer Associated Fibroblasts (Stromal cells) Tumor cells SRK-181 Attributes Targets latent TGFβ-1 Inhibits activation of latent TGFβ-1 across ALL compartments Turns it off at the source Context-Independent: SRK-181 Designed to Inhibit Latent TGFβ-1 Acro
Slide 69: SRK-181 Therapeutic Hypothesis: Potential Advantages
SRK-181 Therapeutic Hypothesis: Potential Advantages of Latent TGFβ-1 Inhibitor 69 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 70: 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 70 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 71: SRK-181-mIgG1 Combination Led to Melanoma Tumor Regression
SRK-181-mIgG1 Combination Treatment Led to Melanoma Tumor Regression and Survival Benefit 71 *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 72: Selectivity of SRK-181 Offers Potential to Overcome Toxicity
Selectivity of SRK-181 Offers Potential to Overcome Toxicity and Dose-limiting Challenges of Non-selective TGFβ Pathway Approaches 72 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 73: 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 74: Biomarker Strategies Employed in DRAGON Trial
Biomarker Strategies Employed in DRAGON Trial 74 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 75: Clear Evidence of Target Engagement: Circulatory TGFβ-1
Clear Evidence of Target EngagementPharmacodynamic Biomarker Results for Part A: Circulatory TGFβ-1 75 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 76: Preclinical Data Support Evaluating Peripheral Samples for SRK-181 Activity
Preclinical Data Provide Scientific Rationale to Evaluate Peripheral Samples for Evidence of SRK-181 Activity 76 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 (June 2023) on 6ix