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): March 13, 2019
Scholar Rock Holding Corporation
(Exact Name of Registrant as Specified in Charter)
| Delaware | 001-38501 | 82-3750435 |
| (State or Other Jurisdiction of Incorporation) | (Commission File Number) | (I.R.S. Employer Identification Number) |
620 Memorial Drive, 2nd Floor, Cambridge, MA 02139
(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:
☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
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. Other Events.
The management of Scholar Rock Holding Corporation (the “Company”) will participate in the Cowen and Company Annual Healthcare Conference in Boston, MA on Wednesday, March 13, 2019 with a presentation at 9:20 a.m. ET and the Oppenheimer Annual Healthcare Conference in New York, NY on Tuesday, March 19, 2019 with a presentation at 3:55 p.m. ET.
A copy of the presentation slide deck that will be presented at both the Cowen and Company Annual Healthcare Conference and Oppenheimer Annual Healthcare Conference is being furnished as Exhibit 99.1 to this Report on Form 8-K. A live webcast of the presentations may be accessed by visiting the Investors & Media section of the Scholar Rock website at http://investors.scholarrock.com.
The information in this Report on Form 8-K 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, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
| 99.1 | Presentation Slide Deck, furnished hereto. |
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 | ||
| Date: March 13, 2019 | By: | /s/ Junlin Ho |
| Junlin Ho | ||
| VP, Head of Corporate Legal | ||
Exhibit 99.1
March 2019 From New Insights to New Medicines
2 Disclaimers Various statements in this presentation concerning Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding its strategy, its product candidate selection and development timing, inclu din g timing for the initiation of and reporting results from its clinical trials for its product candidates, its disease indication selection and timing for such selection, the ability of SRK - 015 to affect the treatment of patients suffering from SMA either as a monotherapy or in conjunction with the current standard of care, the ability of SRK - 181 to affect the treatment of cancer patients in a manner consistent with preclinical data, and the projected use of cash constitute forward - looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. The use of words such as “may,” “might,” “will,” “should,” “expec t,” “plan,” “anticipate,” “believe,” “estimate,” “target,” “project ,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward looking statements. Actual results may differ materially from those indicated by these forw ard - looking statements as a result of various important factors, including, without limitation, Scholar Rock’s ability to provide th e financial support and resources necessary to identify and develop multiple product candidates on the expected timeline, competition from others developing products for similar uses, Scholar Rock’s ability to obtain, maintain and protect its intellectual property , S cholar Rock’s dependence on third parties for development and manufacture of product candidates including to supply any clinical tri als , and Scholar Rock’s ability to manage expenses and to obtain additional funding when needed to support its business activities and es tablish and maintain strategic business alliances and new business initiatives as well as those risks more fully discussed in the sec tio n entitled "Risk Factors" in the Quarterly Report on Form 10 - Q for the quarter ended September 30, 2018, which is on file with the Securiti es and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock’s sub sequent filings with the Securities and Exchange Commission. Any forward - looking statements represent Scholar Rock’s views only as of to day and should not be relied upon as representing its views as of any subsequent date. Scholar Rock explicitly disclaims any obli gat ion to update any forward - looking statements unless required by law. © Scholar Rock, Inc. All rights reserved. March 2019 .
3 2018: Transformative Year for Scholar Rock Established Strong Financial Foundation • Transitioned to public company with successful $86M IPO Transitioned to Clinical - Stage Company • SRK - 015 Phase 1 trial supports advancement to Phase 2 SMA proof - of - concept trial Executed Strategic Collaboration • Gilead fibrosis collaboration with $80M upfront and up to $1.45B in milestones Advanced Innovative Pipeline • Progressed antibody platform for neuromuscular disorders, cancer immunotherapy, fibrosis, and anemias
4 Nature’s Growth Factor Activation Machinery Active form of the growth factor TGF β1 propeptide which forms a “cage” Cage renders the growth factor inactive or “latent ” Shi, M., et al. Nature 474, 7351, 343 - 9 (2011) TGF β Superfamily: More than 30 Related G rowth F actors that Mediate Diverse Biological P rocesses Mature TGF β1 TGF β1 Precursor Complex
5 Program / Target Indication Discovery / Early Preclinical Preclinical Phase 1 Phase 2 Rights / Partner Next Anticipated Milestone INTERNAL PROPRIETARY PROGRAMS Pro/Latent Myostatin SRK - 015 Spinal Muscular Atrophy Initiate Phase 2 POC Trial in 1Q19 SRK - 015 Myostatin - Related Disorders Identify Next Indication in 2020 Latent TGF β SRK - 181 (Context - Independent Latent TGF β 1 ) Oncology/Immuno - oncology Initiate Phase 1 Trial Mid - 2020 Context - Dependent Latent TGF β 1 / Immune Cell Oncology/Immuno - oncology BMP6 BMP6 Signaling Pathway Anemia PARTNERED PROGRAMS Latent TGF β Context - Independent Latent TGF β 1 Fibrosis Context - Dependent Latent TGF β1 / LTBP1 & LTBP3 Fibrosis Undisclosed Program Fibrosis Context - Dependent Latent TGF β1 / GARP Oncology/Immuno - oncology Janssen Biotech, Inc Robust Pipeline Portfolio
SRK - 015: Inhibitor of Myostatin Activation Potential First Muscle - Directed Therapy for SMA
7 SRK - 015: Highly Specific Inhibitor of Latent Myostatin • Myostatin is a genetically - validated, negative regulator of muscle mass expressed in skeletal muscle tissue • Vertebrates lacking the myostatin gene are healthy and display increased muscle mass and strength Vertebrates lacking the myostatin gene are healthy and display increased muscle mass and strength Differentiated approach with SRK - 015: ▪ Fully human monoclonal antibody ( mAb ) ▪ Highly selective inhibitor of the activation of myostatin precursor ▪ Half - life of 23 - 33 d ays ▪ Orphan Drug Designation for SMA granted by FDA and EC ▪ US Patent 9,758,576 covers mAbs that inhibit the activation of the myostatin precursor (expiry in 2034)
8 Traditional Approaches Can Raise Significant Safety Concerns Activin A GDF11 Myostatin BMP9 • Most inhibitors of active myostatin also inhibit GDF11 and may inhibit other growth factors as well • Antibodies to ActRIIb and ligand trap approaches inhibit signaling of multiple ligands GDF11 Deletion Traditional Approaches Lack Selectivity Scholar Rock Approach proMyostatin proActivin A proGDF - 11 Myostatin Activin A GDF - 11 SRK - 015 Exquisite Selectivity By Targeting Precursor Form of Myostatin Kidney formation Reproductive function Angiogenesis
9 Scholar Rock’s Guiding Principles for Neuromuscular Indication Selection Key Characteristics of Spinal Muscular Atrophy (SMA) Younger population Genetic disorder with onset in childhood A t least partially intact innervation and no structural muscle abnormalities Partial neural connectivity and a trophied muscles that largely retain structural integrity Need for increase in fast - twitch muscle fibers Substantial deficit in fast - twitch fibers Clinical trial endpoint driven by fast - twitch fiber function Fast - twitch fiber function has a prominent role in SMA outcome measures SRK - 015: Aligning Therapeutic Approach with Myostatin Biology
10 Significant Unmet Need Remains Despite Current Therapies Mean improvement in HFMSE score experienced by patients with later - onset SMA in the Phase 3 CHERISH clinical trial of nusinersen 0 20 40 60 80 HFMSE Score at Month 15 Mean Baseline Score Mean Improvement with nusinersen Unmet Medical Need for Functional Improvement with Muscle - Directed Therapies Total Possible HFMSE Score of 66 Muscle Function in SMA (Human) Hammersmith Functional Motor Scale Expanded (HFMSE) Address SMN deficiency to p revent further motor neuron deterioration Act directly on muscle with aim to improve functional performance SMN Upregulator Therapies Muscle - Directed T herapies (SRK - 015) SRK - 015 has the potential to drive functional performance across a range of severity observed in SMA either as a monotherapy or in conjunction with any SMN upregulator/corrector therapy
11 Review of Preclinical Data in SMN Δ7 Mouse Models *muSRK - 015P is the parental clone of SRK - 015 on a mouse IgG1 framework Preclinical data published Nov 2018: Long , K., O’Shea, K., Khairallah , R., et al. Specific Inhibition of Myostatin Activation is Beneficial in Mouse Models of SMA Therapy. Human Molecular Genetics, ddy382 Treatment improved muscle mass and strength ▪ Maximal torque of the plantar flexor muscle group increased: ▪ More severe model: 44% - 51% ▪ Less severe model: 20% - 30 % ▪ Achieved multi - fold increase in serum latent myostatin levels indicating target engagement ▪ Confirms presence of target in disease setting ▪ Lower latent myostatin levels in the SMA group may be attributable to reduced overall muscle mass More Severe Model Less Severe Model NA muSRK - 015P* SMN upregulator + muSRK - 015P SMN upregulator only
12 SRK - 015 Phase 1 Trial Design SINGLE - ASCENDING DOSE (SAD) MULTIPLE - ASCENDING DOSE (MAD) Design Subjects Dosing Double - blind, placebo - controlled 3:1 randomization 40 Adult healthy v olunteers (Ages 18 - 55) Double - blind, placebo - controlled 3:1 randomization Single doses at: 1, 3, 10, 20, or 30 mg/kg 26 Adult healthy v olunteers (Ages 18 - 55) Q2W dosing for 3 doses at: 10, 20, or 30 mg/kg KEY OBJECTIVES OF PHASE 1 Evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of SRK - 015 IV
13 Phase 1 Interim Safety Results Support Advancing to Phase 2 Trial • SRK - 015 was well - tolerated with no apparent safety signals • No dose - limiting toxicities identified up to highest evaluated dose of 30 mg/kg - No discontinuations due to a treatment - related AE - No treatment - related SAEs or deaths - No hypersensitivity reactions • Anti - drug antibody tests were negative in SAD; MAD data pending • SAD cohort: AEs * were observed in 30% (9/30) SRK - 015 - vs. 50 % (5/10) placebo - treated subjects - Most frequently reported AE: headache • MAD ** cohort: AEs observed in 30% (6/20) SRK - 015 - vs. 67% (4/6) placebo - treated subjects - Most frequently reported AE: postural dizziness • Single reported SAE of gallstone - induced pancreatitis - Assessed by trial investigator as unrelated to SRK - 015 treatment * The term “adverse event” noted in this presentation refers to a treatment - emergent adverse event, which is defined as an AE with onset after administration of study drug through the final follow - up visit, or in the event that onset time precedes study drug administration, the AE increases in sever ity during the post - dosing follow - up period ** MAD analysis includes data to interim cut - off (Day 35 for 30 mg/kg dose cohort and longer follow - up for 10 and 20 mg/kg dose cohorts)
14 PK Data Support Infrequent Dosing Displayed Well - Behaved PK Profile • Consistent with that commonly observed with monoclonal antibodies • Dose - proportional serum drug exposure Half - Life S upports I nfrequent D osing • Serum half - life of 23 - 33 days across the SRK - 015 dose groups • Supports planned evaluation of once every 4 - week (Q4W) dosing in Phase 2 Pharmacokinetic (PK) Data from Single - Ascending Dose
15 PD Data Demonstrate R obust and Sustained Target Engagement Robust Target Engagement Observed • Marked increases in serum concentrations of latent myostatin following a single dose of SRK - 015 • No meaningful change observed with placebo Evidence Supports Durable Target Saturation • Peak latent myostatin levels plateaued starting with a single dose at 3 mg/kg suggesting target saturation - Single dose at 1 mg/kg only attained approximately half of the peak level • Plateau was sustained demonstrating durability of effect: - T hru Day 28 after single dose at 10 mg/kg dose - Thru at least Day 84 after single doses at 20 and 30 mg/kg Biomarker/Pharmacodynamic ( PD) Data from Single - Ascending Dose Initial proof - of - mechanism in humans of Scholar Rock’s therapeutic approach t argeting the latent form of growth factors
16 EVIDENCE TO DATE Effectively increase motor function to drive clinically meaningful outcomes x Translational/preclinical data support myostatin as a drug target in SMA x Preclinical data demonstrate potential for substantial increases in muscle strength x Interim Phase 1 PD data demonstrate SRK - 015 can successfully engage the target in a durable fashion Safety profile to enable chronic dosing, including in pediatric populations Low drug administration burden to offer broad accessibility x Minimally invasive route of administration (IV) x Interim PK and PD data support an infrequent dosing regimen (e.g . once every 4 weeks ) x Well - tolerated with no apparent safety signals based on Phase 1 interim data x Binds myostatin precursors with high selectivity in vitro GOALS SRK - 015 Target Profile in SMA Emerging evidence supports investigating the safety and efficacy of SRK - 015 in SMA
17 SRK - 015 Opportunity in Spinal Muscular Atrophy Overall Prevalence of 30,000 - 35,000 in U.S. and Europe Potential to use SRK - 015 in conjunction with SMN upregulators Potential to use SRK - 015 as monotherapy or in conjunction with SMN upregulators Relative Prevalence Among Patients Living With SMA Type I 14% Type II 51% Type III 35% Lally et al, Orphanet Journal of Rare Diseases, 2017 Type I: • Infant - onset; often fatal Type II and non - ambulatory type III: • Later - onset but still early childhood • Severe deficits in motor function Ambulatory type III: • Limited mobility and substantial morbidity Type IV: • Population n ot well - characterized Focus of Phase 2 Trial
18 Overview of Phase 2 TOPAZ Trial in SMA • 3 cohorts ; total of 50 - 60 patients • 12 - month treatment period • SRK - 015 IV every 4 weeks (Q4W) Design Subjects Key Objectives Timeline • Type 3 ambulatory SMA (monotherapy or in conjunction with approved SMN upregulator) • Type 2 and Type 3 non - ambulatory SMA (in conjunction with approved SMN upregulator) • Type 2 SMA very young children (in conjunction with approved SMN upregulator) • HFMSE (non - ambulatory SMA) • RHS (ambulatory SMA) • Safety • Preliminary PK/PD by end of 2019 • Interim safety/efficacy analysis in 1H20 • Top - line results 4Q20 - 1Q21 HFMSE – Hammersmith Functional Motor Scale Expanded; RHS – Revised Hammersmith Scale
19 SRK - 015: Path to Top - Line Results in SMA End of 2019 1H 2020 4Q20 - 1Q21 2Q19 1 Q19 Initiate trial - Start - up activities, including contracts and IRB submissions with trial sites Commence patient dosing - Provide additional details of Phase 2 trial design Preliminary PK/PD data from subset of patients - Further assess the pharmacologic profile of SRK - 015 Interim efficacy and safety analysis by cohort - Subset of patients with at least 6 months of treatment exposure Top - line results - F ull 12 - month treatment period by cohort SRK - 015 has the potential to be the first muscle - directed therapy for patients with SMA
TGFβ1: Significant Opportunities in Oncology/Immuno - oncology and Fibrosis
21 TGF β1 Plays Central Role in Multiple Diseases with Unmet Need Oncology Fibrosis Immuno - Oncology Tumor - Directed Therapy Myeloproliferative Disorders
22 Inhibition of TGF β 1: Multipronged Approach for Immuno - Oncology TGF β 1 is a key driver of immune system evasion by cancer cells TGF β 1 Regulatory T cell Tumor Associated Macrophage Cancer Associated Fibroblasts (Stromal cells) Nature (on - line), Feb. 14, 2018 • Pathway analysis points to TGFβ1 as major determinant of resistance to anti - PD - L1 ( atezolizumab ) • TGFβ1 creates ‘immune excluded’ tumor microenvironment • Anti - TGFβ antibody enhances anti - PDL1 treatment response in syngeneic EMT - 6 tumor model Tumor cells
23 TGF β 1 is the Predominant Isoform in Most Human Tumors TGFB1 TGFB2 TGFB3 bladder urothelial carcinoma head & neck squamous cell 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 invasive carcinoma cervical & endocervical cancer cholangiocarcinoma colon adenocarcinoma diffuse large B-cell lymphoma esophageal carcinoma glioblastoma multiforme kidney chromophobe lung squamous cell carcinoma mesothelioma ovarian serous cystadenocarcinoma pancreatic adenocarcinoma pheochromocytoma & paraganglioma prostate adenocarcinoma rectum adenocarcinoma sarcoma testicular germ cell tumor thymoma thyroid carcinoma uterine carcinosarcoma uterine corpus endometrioid carcinoma uveal melanoma scale (% of patient samples (+) for TGFb isoform) 0 20 40 60 80 100 • TGFβ1 prevalent in human cancers for which c heckpoint therapies are approved • Expression data for most tumor types suggest that TGF β signaling mainly driven by TGF β 1 The Cancer Genome Atlas RNAseq analysis: >10,000 samples spanning 33 tumor types
24 TGF β 1 Blockade with SRK - 181 - mIgG1 Renders Preclinical Bladder Tumors Susceptible to Anti - PD1 Therapy Dosing initiated when tumors reached 30 - 80 mm 3 Treatment with RMP1 - 14 anti - PD1 (5mg/kg twice weekly) and/or SRK - 181 - mIgG1 (once weekly at indicated dose) Days after treatment initiation Tumor volume (mm3) Control Anti - PD - 1/ SRK - 181 - mIgG1 ( 10 mg/kg) Anti - PD - 1/ SRK - 181 - mIgG1 ( 3 mg/kg ) SRK - 181 - mIgG1* (10 mg/kg) 0/13 Endpoint Responders 4/14 8/14 0/12 0/13 Anti - PD - 1 • SRK - 181 - mIgG1 is a highly specific inhibitor of TGFβ1 with no meaningful binding to TGFβ2/TGFβ3 • MBT - 2 model is poorly responsive to PD - 1 blockade as a monotherapy • Combination of SRK - 181 - mIgG1 and anti - PD1 resulted in tumor regression or tumor control P reclinical data shown above as presented at Society for Immunotherapy of Cancer (SITC) 33rd Annual Meeting (Nov 2018) * SRK - 181 - mIgG1 was formerly referred to as SRT β1 - Ab3
25 Days after treatment initiation Tumor volume (mm3) Control Anti - PD - 1 Anti - PD - 1/ SRK - 181 - mIgG1 ( 10 mg/kg ) Anti - PD - 1/ SRK - 181 - mIgG1 ( 3 mg/kg ) SRK - 181 - mIgG1* (30 mg/kg) Anti - PD - 1/ SRK - 181 - mIgG1 ( 30 mg/kg ) Endpoint Responders 0/11 0/12 2/12 10/12 7/9 8/11 Anti - TGF β 1 Combination with PD - 1 Blockade is Effective in Preclinical Melanoma Model • Cloudman S91 model is poorly responsive to PD - 1 blockade as a monotherapy • Combination of SRK - 181 - mIgG1 and anti - PD1 resulted in tumor regression or tumor control Interim preclinical data shown above as presented at Society for Immunotherapy of Cancer (SITC) 33rd Annual Meeting (Nov 2018) * SRK - 181 - mIgG1 was formerly referred to as SRT β1 - Ab3
26 Cloudman S91 Melanoma Model 0 10 20 30 40 0 25 50 75 100 Days after treatment initiation Survival (%) SRK - 181 - mIgG1 Combined with Anti - PD1 Therapy Leads to Significant Survival Benefit in Preclinical Tumor Models MBT - 2 Bladder Cancer Model Days after treatment initiation Survival (%) 0 7 14 21 28 0 25 50 75 100 P reclinical data shown above as presented at Society for Immunotherapy of Cancer (SITC) 33rd Annual Meeting (Nov 2018) ** SRK - 181 - mIgG1 was formerly referred to as SRTβ1 - Ab3 * * *** *** * P<0.05 Log - rank ( Mantel - Cox test) *** P<0.001
27 200 µm Control Anti - PD - 1/ SRK - 181 - mIgG1 ( 10 mg/kg) SRK - 181 - mIgG1 * Anti - PD - 1 SRK - 181 - mIgG1 Combination Therapy Enables Infiltration and Expansion of CD8 + T cells in Preclinical Tumor Model IHC of MBT - 2 tumors at day 10 • Marked increase in frequency of CD8 + T cells within the tumor • Consistent with flow cytometry data at day 13 P reclinical data shown above as presented at Society for Immunotherapy of Cancer (SITC) 33rd Annual Meeting (Nov 2018) * SRK - 181 - mIgG1 was formerly referred to as SRT β1 - Ab3
28 TGFβ1 Isoform Specificity of SRK - 181 Results in Improved Preclinical Toxicity Profile • Animals dosed with pan - TGF β inhibitors, LY2109761 (inhibitor of ALK5, common TGF β receptor kinase) or pan - TGF β antibody, exhibited expected cardiac findings based on published data • Exposure as assessed by SRK - 181 serum concentration reached 2,300 µg/ml following 4 weekly doses of 100 mg/kg • No SRK - 181 related adverse effects were noted up to 100 mg/kg per week • No cardiotoxicities ( valvulopathy ) were noted with SRK - 181 • No observed adverse effect level (NOAEL) for SRK - 181 was the highest dose evaluated (100 mg/kg QW) Repeat dose pilot toxicology study in adult female Sprague Dawley rats P reclinical data shown above as presented at Society for Immunotherapy of Cancer (SITC) 33rd Annual Meeting (Nov 2018) Legend Unremarkable Minimal Valvulopathy Slight Atrium - Mixed cell infiltrate Moderate Myocardium - Degeneration/necrosis Myocardium - Hemorrhage Myocardium - Mixed cell infiltrate, base Coronary artery - Necrosis with inflammation Cardiomyocyte - Necrosis/inflammatory cell infiltrate 30 mg/kg Microscopic observations in heart iv, qwk x 4 po, qd x 8 iv, 1 dose iv, qwk x 4 Control SRK-181PanTGFβAbLY2109761 vehicle 10 mg/kg 30 mg/kg iv, qwk x 4 iv, qwk x 4 100 mg/kg300 mg/kg
29 SRK - 181: Advancing Development for Treatment of Cancers Resistant t o Checkpoint Blockade Therapies (CBTs) SRK - 181 is a fully human antibody designed to bind to, and prevent the activation of, latent TGFβ1 with high affinity and high selectivity TGF β signaling Implicated as a culprit in primary resistance to CBTs Translational data analyses TGFβ1 expression is prominent in many human tumor types for which CBTs is approved or showed clinical activity Clinical correlation and preclinical model data TGFβ1 excludes effector cell entry into the tumor and limits immune system access to tumor cells Preclinical studies in syngeneic mouse tumor models resistant to CBT Combination of SRK - 181 - mIgG1* with anti - PD1 led to tumor regression/control and significant survival benefit 28 - day pilot toxicology study in adult rats SRK - 181 showed no observed drug - related toxicity up to a weekly dose of 100 mg/kg for 4 weeks *SRK - 181 - mIgG1 is the murine version of SRK - 181
30 Highlights of Strategic Fibrosis Collaboration with Gilead Upon option exercise, responsible for preclinical and clinical development and commercialization Upfront cash and equity investment: $80 million* One - time preclinical milestone: $25 million Additional development, regulatory, and commercial milestones across 3 programs: Up to $1,425 million High single - to low double - digit tiered royalties on net sales *Includes $30 million purchase of Scholar Rock common stock at price per share of $30.60 Responsible for antibody discovery and preclinical research thru product candidate nomination for three TGF β programs Retains exclusive worldwide rights to develop certain TGF β antibodies for oncology and cancer immunotherapy Collaborating to Develop Innovative Therapies for Fibrotic Diseases
31 Upcoming Key R&D Milestones SRK - 01 5 o Initiate Phase 2 SMA proof - of - concept trial by the end of 1Q19 o Commence patient dosing in Phase 2 SMA proof - of - concept trial in 2Q19 o Present full Phase 1 results at a scientific conference in 2019 o Continue to evaluate selective inhibitors of myostatin activation in multiple disease models o Identify next indication in 2020 o Announce Phase 2 trial read - outs: • P reliminary PK/PD analysis by end of 2019 • Interim efficacy and safety analysis at 6 months in 1H20 • Top - line results of 12 - month treatment period 4Q20 - 1Q21 TGFβ1 Inhibitor o Advance cancer immunotherapy product candidate, SRK - 181, into a Phase 1 trial mid - 2020 o Continue to advance active discovery programs for context - dependent inhibition of TGFβ1 o Conduct fibrosis discovery and preclinical studies in partnership with Gilead Cash, cash equivalents, and marketable securities at December 31, 2018: ~$176 million Sufficient to fund operations into 2021
32 Building Value in All Dimensions Executing Strategic Collaboration Advancing Clinical Development Growing Innovative Pipeline Leveraging Strong Financial Foundation