Capricor Therapeutics, Inc. · NASDAQ:CAPR
Capricor Therapeutics — Technical Presentation (March 2018)
164 slides from Capricor Therapeutics's technical presentation, Mar 12, 2018
Slide 1: KOL Lunch on DMD
│ Capricor, Inc. │KOL Lunch on DMD Key Opinion Leaders Lunch to discuss the emerging clinical paradigm in DMD focusing on gene and cell therapy. March 9, 2018 NASDAQ: CAPR
Slide 2: Forward-Looking Statements
│ Capricor , Inc. │KOL Lunch on DMD Forward - Looking Statements Statements in this presentation regarding the efficacy, safety, and intended utilization of Capricor's product candidates ; the initiation, conduct, size, timing and results of discovery efforts and clinical trials ; the pace of enroll
Slide 3: Capricor KOL Speakers
│ Capricor, Inc. │KOL Lunch on DMD • Linda Marban, Ph.D. – Chief Executive Officer, Capricor Therapeutics, Inc. • Deborah Ascheim, M.D. – Chief Medical Officer, Capricor Therapeutics, Inc. • Craig McDonald, M.D., is professor and chair of the Department of Physical Medicine and Rehabilitation and Di
Slide 4: Capricor's Mission
│ Capricor , Inc. │KOL Lunch on DMD Capricor’s Mission Capricor is focused on the discovery, development and commercialization of innovative cell and exosome based therapies for patients with immune - inflammatory rare diseases with a focus on Duchenne muscular dystrophy . 4
Slide 5: Treatment Options for DMD are Limited
│ Capricor , Inc. │KOL Lunch on DMD Treatment Options for DMD are Limited Challenges ▪ EXONDYS 51 – 13% of DMD population ▪ Gene therapy not always effective due to antibody response ▪ Steroids have adverse long term side - effects ▪ NF - kB inhibition may not be enough to mediate immune response ▪
Slide 6: Capricor's CAP-1002 Technology
│ Capricor , Inc. │KOL Lunch on DMD ‒ CAP - 1002 is a biologic consisting of allogeneic cardiosphere - derived cells (CDCs) ▪ Manufactured from donated heart muscle ▪ Does not act by “stemness” – the cells do not engraft into host tissue ▪ MOA: cells secrete EVs (exosomes) » Contain non - coding RNA
Slide 7: Physiological Effects of CDCs in mdx Model
│ Capricor , Inc. │KOL Lunch on DMD Physiological Effects of CDCs in mdx Model RESTORED mitochondrial ultrastructure NORMALIZED deficient respiratory capacity of isolated mitochondria Oxidative Stress phospho - Akt Nrf2 (cytoplasmic) Nrf2 (nuclear) HO - 1 catalase SOD - 2 GCLC cat. sub
Slide 8: Intramyocardial CDC methods
Intramyocardial CDC methods • Mouse model of DMD - 10 m/o mdx mice (n=12 per group) - Randomized to CDC vs vehicle - Followed for 6 months or longer - Single or repeat injection at 3 mo as noted • CDCs - From background mouse strain (C57BL/10) - Injected intramyocardially (LV; 4 injection sites) Ami
Slide 9: Improved function & survival in mouse model
Improved cardiac function Increased exercise capacity Increased survival rate Improved function & survival in mouse model Aminzadeh et al, Stem Cell Reports 2018 ( http://www.cell.com/stem - cell - reports/fulltext/S2213 - 6711(18)30049 - 3 ). 9
Slide 10: Physiological Effects of CDCs in mdx Model
│ Capricor , Inc. │KOL Lunch on DMD Physiological Effects of CDCs in mdx Model Oxidative Stress phospho - Akt Nrf2 (cytoplasmic) Nrf2 (nuclear) HO - 1 catalase SOD - 2 GCLC cat. sub. Inflammation phospho - IkB p65 (nuclear) MCP1 CD68+ macrophages CD3+ T cells NF - kB Aminza
Slide 11: Oxidative stress & inflammation: major players in DMD
Oxidative stress & inflammation: major players in DMD Inflammatory cell infiltration Oxidative stress Aminzadeh et al, Stem Cell Reports 2018 ( http://www.cell.com/stem - cell - reports/fulltext/S2213 - 6711(18)30049 - 3 ). 11
Slide 12: Physiological Effects of CDCs in mdx Model
│ Capricor , Inc. │KOL Lunch on DMD Physiological Effects of CDCs in mdx Model Oxidative Stress phospho - Akt Nrf2 (cytoplasmic) Nrf2 (nuclear) HO - 1 catalase SOD - 2 GCLC cat. sub. Inflammation phospho - IkB p65 (nuclear) MCP1 CD68+ macrophages CD3+ T cells NF - kB Fibros
Slide 13: Reduced cardiac collagen content and fibrosis
Mdx+Vehicle CTL(WT) Mdx+CDC Reduced cardiac collagen content and fibrosis 0.4 0.45 0.5 0.55 0.6 0.65 0.7 CTL Mdx+Vehicle Mdx+CDC CTL(WT) CDC Vehicle † 0.3 0.33 0.36 0.39 0.42 0.45 0.48 0.51 CTL Mdx+Vehicle Mdx+CDC Collagen III A1 † CTL(WT) CDC Vehicle Collagen III A1 Collagen I A1 Collagen I A1 Amin
Slide 14: Physiological Effects of CDCs in mdx Model
│ Capricor , Inc. │KOL Lunch on DMD Physiological Effects of CDCs in mdx Model RESTORED mitochondrial ultrastructure NORMALIZED deficient respiratory capacity of isolated mitochondria Oxidative Stress phospho - Akt Nrf2 (cytoplasmic) Nrf2 (nuclear) HO - 1 catalase SOD - 2 GCLC cat. sub
Slide 15: Restoration of mitochondrial integrity
CTL(WT) Mdx+Vehicle Mdx+CDC Restoration of mitochondrial integrity Aminzadeh et al, Stem Cell Reports 2018 ( http://www.cell.com/stem - cell - reports/fulltext/S2213 - 6711(18)30049 - 3 ). 15 │ Capricor , Inc. │KOL Lunch on DMD
Slide 16: Physiological Effects of CDCs in mdx Model
│ Capricor , Inc. │KOL Lunch on DMD Physiological Effects of CDCs in mdx Model RESTORED mitochondrial ultrastructure NORMALIZED deficient respiratory capacity of isolated mitochondria Oxidative Stress phospho - Akt Nrf2 (cytoplasmic) Nrf2 (nuclear) HO - 1 catalase SOD - 2 GCLC cat. sub
Slide 17: Cardiomyogenesis
0 0.001 0.002 0.003 0.004 0.005 0.006 0.007 CTL Mdx+Vehicle Mdx+CDC 0 0.001 0.002 0.003 0.004 0.005 0.006 0.007 CTL Mdx+Vehicle Mdx+CDC WGA Aurora B DAPI WGA Ki67 DAPI Mdx+Vehicle Mdx+CDC CTL(WT) † † Ki67+ Cardiomyocytes/ Cardiomyocytes in HPF Aurora B+ Cardiomyocytes/ Cardiomyocytes in HPF Cardiomy
Slide 18: Exosomes: CDCs MoA Defined
20 25 30 35 40 45 50 1 15 30 LVEF (%) Days (after MI) CDC-DMSO CDC-GW4869 * CDC exosomes ↑ EF Ibrahim et al., Stem Cell Reports 2014 Exosomes: CDCs MoA Defined • 30 - 150 nm particles • Present in all body fluids • Released by nearly all cell types • Loaded with miRs and other bioactive contents • P
Slide 19: Intramyocardial exosomes recap effects of CDCs
Collagen content Cardiomyogenesis Intramyocardial exosomes recap effects of CDCs Functional benefit on heart Aminzadeh et al, Stem Cell Reports 2018 ( http://www.cell.com/stem - cell - reports/fulltext/S2213 - 6711(18)30049 19 │ Capricor , Inc. │KOL Lunch on DMD
Slide 20: Intravenous CDC methods
Intravenous CDC methods • Mouse model of DMD - 10 - 12 m/o mdx mice - Randomized to CDC vs vehicle - Followed for 3 - 26 weeks - EF, exercise capacity, isolated muscle function • CDCs - From background mouse strain (C57BL/10) - 250k cells infused via jugular vein Adapted from Cedars - Sinai Medical
Slide 21: Biodistribution and Clearance of IV CAP-1002
│ Capricor , Inc. │KOL Lunch on DMD Biodistribution and Clearance of IV CAP - 1002 Biodistribution Clearance Mouse model : WT mice CDCs : Human, 150K Route : Jugular vein Mouse model : SCID mice CDCs : Human, 150K Route : Jugular vein Capricor unpublished data 21
Slide 22: Cardiac, skeletal, and isolated muscle function after IV CDCs
Cardiac, skeletal, and isolated muscle function after IV CDCs V e h i c l e C D C 3 w k C D C 6 w k 0 40 50 60 70 E j e c t i o n F r a c t i o n ( % ) Pre-Treatment Post-Treatment * * V e h i c l e C D C 3 w k C D C 6 w k 0 200 250 300 350 400 450 500 E x e r c i s e C a p a c i t y ( m ) * Post-Tr
Slide 23: Phase I/II HOPE-Duchenne Clinical Trial
│ Capricor , Inc. │KOL Lunch on DMD Phase I / II HOPE - Duchenne Clinical Trial CAP - 1002 (1 x 75M cells) Usual Care n=12 25 patients Ages 12 and older DMD heart disease EF > 35% Stable steroids n=13 6 CAP - 1002 given by intracoronary infusion 12 data presented at AHA 2017 late - breaking session
Slide 24: Baseline Characteristics
│ Capricor , Inc. │KOL Lunch on DMD Baseline Characteristics Usual Care (n=12) CAP - 1002 (n=13) Age, median years (range) 17.5 (12 – 20) 18 (14 – 25) Wheelchair Use Always (%) 7 (58) 10 (77) Cardiac Scar Size, mean % (SD) 21.4 (10.8) 17.6 (6.8) LV Ejection Fraction, mean % (SD) 48.4 (7.5) 49.6 (6.7
Slide 25: Heart Muscle: Reduced Myocardial Scarring
│ Capricor , Inc. │KOL Lunch on DMD Heart Muscle: Reduced Myocardial Scarring ‒ Assessed by cardiac MRI with blinded analysis by core lab ‒ Scar increased in the Usual Care group, but decreased in the CAP - 1002 group ▪ 11.9% group difference in change score at Month 12 (p=0.03) ‒ Decreased scar is
Slide 26: Heart Muscle: Increased Regional Systolic Wall Thickening
│ Capricor , Inc. │KOL Lunch on DMD Heart Muscle: Increased Regional Systolic Wall Thickening ‒ Measurement of cardiac function by MRI allows focus on treated areas ‒ Magnitude of scar reduction is consistent with natural history of scar progression in DMD ▪ Inferior → Anterior → Lateral → Septal ‒
Slide 27: Skeletal Muscle: PUL Results Indicate Functional Benefit
│ Capricor , Inc. │KOL Lunch on DMD Skeletal Muscle: PUL Results Indicate Functional Benefit ‒ Performance of the Upper Limb (PUL) test is a validated instrument in DMD ▪ Relates to patients’ ability to perform common activities of daily living ‒ Trends towards improvement observed throughout follow
Slide 28: HOPE-2 Clinical Trial of CAP-1002
│ Capricor , Inc. │KOL Lunch on DMD — Potential registration trial plan to initiate in 1Q 2018 ▪ Randomized, double - blind, placebo - controlled ▪ Target enrollment of 84 patients with advanced disease ▪ Peripheral intravenous delivery – supported by preclinical studies ▪ Repeat - dose design – pot
Slide 29: Emerging genetic therapies for DMD
Emerging genetic therapies for DMD Jeffrey S. Chamberlain, Ph.D. McCaw Endowed Chair in Muscular Dystrophy Director, Sen. Paul D. Wellstone Muscular Dystrophy Research Center Depts. of Neurology, Medicine and Biochemistry University of Washington Seattle, WA USA Disclosures: JSC is a member of the s
Slide 30: Gene Therapy – different types
Gene Therapy – different types Gene replacement therapy: deliver a new version of a gene to the target tissue (aka gene addition) Gene editing: directly modify a gene to fix or bypass a mutation - CRISPR/Cas9 Gene knockdown: Suppress the activity of a mutant gene - Inhibitory RNA (siRNA, shRNA
Slide 31: Why gene therapy?
Why gene therapy? Fix the primary cause of genetic disorders Potential for a permanent treatment Genetic manipulation of stem cells Overcome genetic errors that lead to cancer Powerful approach to developing new vaccines | Capricor, Inc. │KOL Lunch on DMD 31
Slide 32: Delivering gene therapy to the body
Delivering gene therapy to the body ‘Viral’ Vectors: modified from viruses, no longer “virus” – Adeno - associated viral vectors (AAV) – best for non - dividing cells – Lentiviral vectors – best for dividing cells (e.g. stem cells) – Adenoviral vectors – mostly now used for vaccines, cancer Non
Slide 33: Duchenne muscular dystrophy (DMD)
Duchenne muscular dystrophy (DMD) Most common form of muscular dystrophy (>300,000 cases) Caused by mutations in the 2.2 MB dystrophin gene X - linked, recessive inheritance 1/3 of cases due to new mutation; thousands of independent mutations | Capricor, Inc. │KOL Lunch on DMD 33
Slide 34: Strategies for the development of DMD therapies
Strategies for the development of DMD therapies l Viral vector delivery of genes to muscles Dystrophin replacement Delivery of a surrogate gene ( e.g. Utrophin; GALGT2 ) Transcript modification - bypass mutation Gene editing ( e.g . CRISPR/Cas9) l Antisense oligonucleotide delivery (exon ski
Slide 35: Gene Therapy for DMD/BMD
Gene Therapy for DMD/BMD Goal: Develop methods to replace or repair dystrophin gene Pros: – Fixes the primary cause of the disease – lack of dystrophin – Should work for ALL patients Cons: – Requires bodywide (systemic) gene delivery to muscle AAV vectors ? Potential: – DMD (severe) - no d
Slide 36: Challenges for gene therapy for DMD/BMD
Challenges for gene therapy for DMD/BMD How can you deliver a new gene to muscles, bodywide , in a safe and effective manner? – Development of delivery VECTORS by manipulating viruses – Remove viral genes, replace with gene of interest ( e.g. dystrophin) Vectors derived from adeno - associated v
Slide 37: Assembly of the dystrophin-complex by micro-Dys
Assembly of the dystrophin - complex by micro - Dys 14 kb cDNA 3.7 kb cDNA | Capricor, Inc. │KOL Lunch on DMD 37
Slide 38: Adeno-associated viral (AAV) vectors
Adeno - associated viral (AAV) vectors Non - integrating vectors, persist as episomes PROS : – Numerous serotypes, many target muscle (AAV6, 8 & 9) – Relatively easy to produce; scalable to bioreactor production – Can be used for bodywide gene delivery , especially to muscles CONS : – Small carrying
Slide 39: Systemic gene transfer to muscle using AAV6
Systemic gene transfer to muscle using AAV6 Single tail vein injection of AAV/alkaline phosphatase into adult mice Gregorevic & Chamberlain, Nature Medicine, 2004 Whole mounts stain - 2 mos pi Histochemical stain - 2 years pi AAV holds 5 kb; dystrophin gene = 2.2 MB 39
Slide 40: Development of micro-Dystrophins
Development of micro - Dystrophins “mini” - Dystrophins modified from a very mildly affected BMD patient “Micro - dys” made by systematically removing additional protein domains Many micro - dystrophins made by my lab and some others “H2 - microDys” and “micro - Dys5” entering clinical trials | Capr
Slide 41: Expression of micro-Dystrophin one year after AAV infusion
wildtype dko Tdko Forelimb Masseter Heart Diaphragm Quadriceps Tibialis Ant. Gastroc. Expression of micro - Dystrophin one year after AAV infusion into dystrophic mice (IV) Treated gastrocnemius dystrophin Gregorevic, Nat Med, 2006 41
Slide 42: MicroDys stably expressed years after AAV infusion
MicroDys stably expressed 2 years after AAV infusion in mdx mice - diaphragm muscles 42
Slide 43: DGC expression in GRMD dogs following SGT-001 infusion
GRMD Biceps Brachii 1E13 vg/kg 2E14 vg/kg Microdystrophin β - Sarcoglycan Merge 1E14 vg/kg DGC expression in GRMD dogs following systemic SGT - 001 infusion Kornegay et al | Capricor, Inc. │KOL Lunch on DMD 43
Slide 44: SGT-001 increases force in GRMD dogs
SGT - 001 (AAV - µDys) increases force in GRMD dogs following systemic delivery Kornegay et al Analysis of torque produced by extension and flexion of the tibiotarsal joint. *p<0.05 44
Slide 45: AAV-mediated gene therapy for DMD/BMD
AAV - mediated gene therapy for DMD/BMD Micro - dystrophins halt muscle wasting, protect from exercise - injury and improve strength Not all µDys are equivalent Efficient systemic delivery of AAV/µDys in dogs No reduction in µDys expression after at least 2 years High dose AAV9 delivery ha
Slide 46: Clinical trials planned / in progress
Clinical trials planned / in progress Solid Biosciences - Ganot et al (Chamberlain uDys - 3 rd gen); AAV9 Nationwide Children’s – J Mendell et al (Sarepta) (Chamberlain uDys - 1 st gen); AAV - rh74 Genethon – G Dickson (Sarepta) (Chamberlain uDys - 1 st gen); AAV8 Pfizer – Samulski et al (Xi
Slide 47: Gene therapy
Gene therapy Difficulty of transitioning from academics to clinic Growing, large interest by Biotech and Venture Capitol communities American Society for Gene and Cell Therapy is the premier meeting Future: Gene editing with CRISPR/Cas9? Safety/efficacy? New vectors? Scaling production
Slide 48: Gene therapy options/alternatives?
Gene therapy options/alternatives? Delivery/upregulation of Utrophin (Summit) – AAV/µ Utrn : Chamberlain Overexpression of GALGT2 (NCH trial imminent) – Modifies dystroglycan to assemble a Utrophin - complex Stem cells: e.g. Capricor – Modulate muscle environment/enhance regeneration – Provide
Slide 49: Chamberlain Lab acknowledgements
Chamberlain Lab: Katrin Hollinger – 3 rd gen µDys Julian Ramos – 3 rd gen µDys Julie Crudele - µDys/immunology James Allen – AAV Christine Halbert – AAV Matt Karolak – DGC Maja Zavaljevski – DMD/FSHD/DM1 Darren Bisset - DMD/FSHD/DM1 Niclas Bengtsson – Cas9 John Hall – Sat cells/Cas9/FSHD Aisha Musht
Slide 50: Outcome Measures in DMD Clinical Trial Considerations
OUTCOME MEASURES IN DMD CLINICAL AND TRIAL CONSIDERATIONS PRESENTED BY : MICHELLE EAGLE | Capricor, Inc. │KOL Lunch on DMD
Slide 51: Outcome Measures in DMD
OUTCOME MEASURES IN DMD • Tools/assessments used to: • Evaluate the baseline status of a patient • Evaluate the effect of an intervention • M onitor disease progression • Inform clinical decision making regarding initiation/change of therapies • Clinic or clinical trial context 51 | Capricor, Inc. │
Slide 52: What makes a good outcome measure?
WHAT MAKES A GOOD OUTCOME MEASURE? • Reliable • Excellent inter - rater and intra - rater reliability • Low measurement error • Valid • The degree to which an assessment measures what it intends to • Sensitive • Responsive in the ability to detect meaningful, real changes 52 | Capricor, Inc. │KOL Lu
Slide 53: Qualities of good outcome measures
QUALITIES OF GOOD OUTCOME MEASURES • Meaningful • Clinical meaningfulness • Cost efficient • Easy to administer • Standardised 53 | Capricor, Inc. │KOL Lunch on DMD
Slide 54: Assessment
54 | PRESENTATION TITLE SECOND LINE PROBLEMS ASSESSMENT • Functional Scales – North Star, PUL • EK Scale • timed tests – 10 metre, rise from floor, 6 MWT • muscle strength - MMT, myometry , QMT • Range of movement • Respiratory - FVC, MIP/MEP, PCF • Loss of function • Weakness • Contractures • Immob
Slide 55: Current outcome measures used in DMD
CURRENT OUTCOME MEASURES USED IN DMD ▪ North Star Ambulatory Assessment ▪ PUL (Performance upper limb) ▪ Egen Klassification (EK) ▪ 9 Hole peg test ▪ 6MWT ▪ Timed functional tests ▪ Timed up and go ▪ Rise from floor ▪ Climb/descend stairs ▪ Run/walk 10 metres ▪ ACTIVE seated ▪ Pulmonary Function Tes
Slide 56: Progression of disease over time
PROGRESSION OF DISEASE OVER TIME 56 | Capricor, Inc. │KOL Lunch on DMD
Slide 57: OM's
OM’S • A single outcome is unlikely to cover the breadth of the disease from highly ambulant to wheelchair dependent with limited hand function • Rates of change may vary for upper and lower limb function • Careful balance between asking the impossible and the ultra easy • Some OM have been develope
Slide 58: Progressive improvement in understanding OM's
PROGRESSIVE IMPROVEMENT IN UNDERSTANDING OM’S • We understand more about the relationship between strength and function • That the individual may not represent the population • That OMs do not always correlate highly throughout the disease progression and that some OMs are more useful at different s
Slide 59: Decision framework for inclusion of clinical outcome measures
The table shows the application of outcome measures relevant for DMD in relation to age and validation status ( ✓ ). To be validated (?). Lynn et al. Neuromuscul Dis 2014;25:96 – 105 DECISION FRAMEWORK FOR INCLUSION OF CLINICAL OUTCOME MEASURES IN PHASE II/III TRIALS 59
Slide 60: Total PUL scores by age
Fig. 2 Total PUL scores in ambulant (blue) and non ambulant (red) DMD patients plotted according to age. Pane et al. 2014 http://dx.doi.org/10.1016/j.nmd.2013.11.014 60 | Capricor, Inc. │KOL Lunch on DMD
Slide 61: Ambulatory assessments
AMBULATORY ASSESSMENTS NSAA/ 6 MWT/ TIMED FUNCTION TESTS | Capricor, Inc. │KOL Lunch on DMD
Slide 62: Loss of ambulatory function occurs in a predictable way
LOSS OF AMBULATORY FUNCTION OCCURS IN A PREDICTABLE WAY • Unable to jump, hop and run • Gowers’ sign with standing • Loss of standing from the floor • Loss of lie to sit • Loss of stair climbing • Loss of ability to stand from a chair • Loss of ability to walk independently (10 meter walk/run; 6MWD)
Slide 63: North Star Ambulatory Assessment
North Star Ambulatory Assessment 63
Slide 64: North Star Ambulatory Assessment
NORTH STAR AMBULATORY ASSESSMENT Sit to stand Descend step | Capricor, Inc. │KOL Lunch on DMD 64
Slide 65: Jump Gets to sit
Jump Gets to sit | Capricor, Inc. │KOL Lunch on DMD 65
Slide 66: 6MWT
6MWT • Adapted/validated for DMD (McDonald 2010) • Regulator approved • Minimally clinically important difference considered 30 meters • Correlates with: • Knee extension strength • 10 minutes continuous step activity • Number of challenges conducting test, especially with younger and more cognitive
Slide 67: 6-Minute Walk Test
6 - MINUTE WALK TEST • 6MWT: popular primary outcome measure • Other primary outcome measures exist, including 4 - stair climb • E Mercuri showed that if the distance walked in 6 minutes is at least 330 metres at baseline, the risk of losing ambulation within 2 years is significantly reduced ( Mazzo
Slide 68: Strength testing
STRENGTH TESTING | Capricor, Inc. │KOL Lunch on DMD
Slide 69: Manual Muscle Testing (MMT)
MANUAL MUSCLE TESTING (MMT) • MRC scale • Reliable in patients with NMD when conducted by experienced evaluators • Issues with differentiating between higher grades: • Importance of practice and experience • Cheap/easy to conduct 69 | Capricor, Inc. │KOL Lunch on DMD
Slide 70: Hand held myometry
HAND HELD MYOMETRY • Variety of myometers available: • Microfet • Make test • Explanation/demonstration/prac tice • Key muscle groups • Standardised testing positions and myometer placement • Best of 3”valid” efforts • Repeat if patient moves out of position or doesn’t gives a submaximal effort • En
Slide 71: Quantitative muscle testing systems
QUANTITATIVE MUSCLE TESTING SYSTEMS CINRG CQMS 71 | Capricor, Inc. │KOL Lunch on DMD
Slide 72: Assessments for non-ambulant
ASSESSMENTS FOR NON - AMBULANT | Capricor, Inc. │KOL Lunch on DMD
Slide 73: Non-ambulatory milestones – Egen Klassifikation scale
NON - AMBULATORY MILESTONES – EGEN KLASSIFIKATION SCALE • The EK scale is a good clinical tool – each question can help to formulate requirements for treatment or adaptations • Highly clinically meaningful but less sensitive to change over the short term • Loss of ability to turn in bed • Loss of he
Slide 74: Need for upper limb assessment tool
Prior to this publication in 2012 there were numerous workshops and discussions on existing measures Need for a tool that could assess upper limb function across the lifespan 74 | Capricor, Inc. │KOL Lunch on DMD
Slide 75: Non-ambulatory milestones
NON - AMBULATORY MILESTONES ▪ Loss of ability to reach over head ▪ Loss of ability to reach the scalp ▪ Loss of ability to self - feed without adaptations (hand to mouth) ▪ Loss of ability to place hands to table top ▪ Loss of ability to use a computer (distal hand function) • Performance of Upper L
Slide 76: 76 | Capricor, Inc. │KOL Lunch on DMD
76 | Capricor, Inc. │KOL Lunch on DMD
Slide 77: Conceptual framework
CONCEPTUAL FRAMEWORK | Capricor, Inc. │KOL Lunch on DMD 77
Slide 78: Dimensions + items
DIMENSIONS+ ITEMS | Capricor, Inc. │KOL Lunch on DMD 78
Slide 79: Version 1.1, 1.2 and now 2.0
Version 1.1, 1.2 and now 2.0 79 | Capricor, Inc. │KOL Lunch on DMD
Slide 80: PUL Items
PUL ITEMS Shoulder domain mid level - domain | Capricor, Inc. │KOL Lunch on DMD 80
Slide 81: PUL Items
PUL ITEMS Bilateral activity Distal domain | Capricor, Inc. │KOL Lunch on DMD 81
Slide 82: FOO!
FOO! SELF-CARE LEISURE AND COMMUNICATION Cando | Candowith | Impossible ESTEEM easily difficulty | without help 22 | Use a TV remote control ible 1 |, ut 23. | Dial / text on a cell phone 2 1 2 116 | open al 2 | Bring phone to your ear 3 10 25 | Type on a computer with a keyboard 17 | Opena 4 |u 26
Slide 83: Respiratory function tests
RESPIRATORY FUNCTION TESTS | Capricor, Inc. │KOL Lunch on DMD
Slide 84: Respiratory function
RESPIRATORY FUNCTION • Respiratory function (RF) and survival are strongly associated • Most frequently, both in clinics and in trials, forced vital capacity is measured • Milestones include time to ventilation and death • Other commonly used measures are maximal inspiratory pressure, maximal expira
Slide 85: Survival in Duchenne muscular dystrophy: 1967–2002
Survival in Duchenne muscular dystrophy: 1967 – 2002 0 5 10 15 20 25 30 0.0 0.2 0.4 0.6 0.8 1.0 Died in 60s Died in 70s Died in 80s Died in 90s not ventilated ventilated in 90s age at death %survival Mean age of death vent + SS vent 1990s 1980s 1970s 1960s CM 10 11 12 13 14 15 16 17 18 19 20 21 22 2
Slide 86: Outcome measures across the lifespan
NORTH STAR AMBULATORY ASSESSMENT 6 MINUTE WALK TEST TIMED FUNCTION TESTING Performance of upper limb Performance of upper limb/EK SCALE MUSCLE STRENGTH TESTING RESPIRATORY FUNCTION TESTING AMBULANT TRANSITIONAL NON AMBULANT YOUNGER LIFETIME OLDER 86 | Capricor, Inc. │KOL Lunch on DMD
Slide 87: Thank you
Thank you | Capricor, Inc. │KOL Lunch on DMD
Slide 88: Duchenne Muscular Dystrophy: Overview, Natural History, and Unmet Need
Duchenne Muscular Dystrophy: Overview, Natural History, and Unmet Need Craig McDonald, MD Professor of PM&R and Pediatrics Study Chair CINRG Duchenne Natural History Study University of California Davis Medical Center Sacramento, CA | Capricor, Inc. │KOL Lunch on DMD 8 8
Slide 89: Disclosures
Disclosures ‣ Consulting work on Duchenne muscular dystrophy clinical trials for – Capricor Therapeutics, Inc. – Catabasis Pharmaceuticals, Inc. – PTC Therapeutics – Sarepta – Prosensa – Pfizer – Eli Lilly – Bristol Myers Squib – Italfarmaco – Mitobridge – Cardero Therapeutics | Capricor, Inc. │KOL
Slide 90: DMD Is a Devastating Progressive Disease with Significant Unmet Need
Duchenne Muscular Dystrophy Is a Devastating Progressive Disease with Significant Unmet Need ‣ Rare recessive x - linked disorder caused by mutation in the DMD gene ‣ Leads to dystrophin deficiency in muscle tissue and subsequently chronic activation of NF - kB ‣ Progressive disease that leads to de
Slide 91: Disease Progression: Muscle Damage and Fat Infiltration
Disease Progression Is Characterized by Muscle Damage and Replacement of Muscle Fibers with Fat Infiltration and Sclerosis, Resulting in Loss of Function Normal muscle tissue Muscle tissue 19 year old DMD patient Post - Mortem Fat infiltration, sclerotic changes and loss of muscle fibers Lack of dys
Slide 92: Loss of Muscle Fiber in DMD
Loss of Muscle Fiber in DMD: Normal 3 year old 9 year old 19 year old (Post - Mortem in Year 1990) Post - Mortem Serum CK | Capricor, Inc. │KOL Lunch on DMD 9 2
Slide 93: DMD pathomechanism
DMD pathomechanism Adapted from Engvall & Wewer (2003) FASEB 17:1579 Structural defect Membrane instability Apoptosis / Necrosis Inflammation Fibrosis Fiber Death | Capricor, Inc. │KOL Lunch on DMD 9 3
Slide 94: Motor and Cognitive Assessment of Infants and Young Boys with DMD
Motor and Cognitive Assessment of Infants and Young Boys with Duchenne Muscular Dystrophy: Results from the Muscular Dystrophy Association DMD Clinical Research Network. Connolly et al. (n=25; 1.8 ± 0.8 years) | Capricor, Inc. │KOL Lunch on DMD 9 4
Slide 95: Neck Flexion Weakness
• Neck Flexion Weakness one of earliest clinical signs • 2 years, 10 months | Capricor, Inc. │KOL Lunch on DMD 9 5
Slide 96: | Capricor, Inc. │KOL Lunch on DMD 9 6
| Capricor, Inc. │KOL Lunch on DMD 9 6
Slide 97: Early Gower's Sign
Early Gower ’ s Sign (2 yr 10 mo) | Capricor, Inc. │KOL Lunch on DMD 9 7
Slide 98: Baseline Assessment of Young Boy
9 Year Old Boy: Baseline Assessment Rise From Floor 7 Sec; 6MWD 414 Meters | Capricor, Inc. │KOL Lunch on DMD 9 8
Slide 99: Case Study: Assessment in 2007
Case Study: 9 Year Old Boy: Assessment in 2007 Rise From Floor 13 Sec; 6MWD 330 Meters | Capricor, Inc. │KOL Lunch on DMD 9 9
Slide 100: Case Study: Assessment in 2007
DMD Patient Age 9.5 10 - meter Walk/Run = 6.5 s 6MWD = 330 Meters Case Study: 9 Year Old Boy: Assessment in 2007 10 meter run / walk = 6.5 seconds; 6MWD 330 Meters | Capricor, Inc. │KOL Lunch on DMD 100
Slide 101: Case Study: Burden of Disease
Case Study: Burden of Disease Same Young man aged 17 Assessment 2015 | Capricor, Inc. │KOL Lunch on DMD 101
Slide 102: Contemporary Treatments that have Affected Natural History
Contemporary Treatments that have Affected the Natural History of Disease Progression and Survival in DMD 1. Glucocorticoids 2. Management of spine deformity – Glucocorticoids – Timely spine surgery for curves >30 to 40 degrees 3. Pulmonary management – Airway clearance strategies/mechanical cough a
Slide 103: CINRG Data: Loss of Ambulation
CINRG Data: Loss of Ambulation (all mutation subtypes and steroid use, N = 309) 0.00 0.25 0.50 0.75 1.00 0 5 10 15 20 Age (years) <30 days cumulative GC exp 1 year or greater cumulative GC exposure Kaplan-Meier survival estimates > 1 year steroids: • Median LOA = 13.3 ± 0.3 yrs • 95% CI = 12.5 – 14
Slide 104: Changing Natural History in DMD Over 4 Decades
There Has Been a Changing Natural History in DMD Over the Last 4 Decades Affecting Survival 1960 s No Treatment Passamano , et al. Acta Myol . 2012;31(2):121 - 125. Eagle, et al. Neuromuscul Disord . 2007;17(6):470 - 475. 1970 - 1990 Spine Surgery & Ventilation | Capricor, Inc. │KOL Lunch on DMD 104
Slide 105: DMD Survival Affected Primarily by Ventilation
DMD Survival Affected Primarily by Ventilation • Ventilation was recognized as a main intervention affecting survival • Ventilated median survival = 27.0 yr • Without ventilation = 19.0 yr Passamano, et al. Acta Myol . 2012;31(2):121 - 125. • Ventilation was recognized as a main intervention affecti
Slide 106: Changing Natural History in DMD Over 4 Decades
There Has Been a Changing Natural History in DMD Over the Last 4 Decades Affecting Survival 1980 s – Present Glucocorticoids/Steroids Schram, et al. J Am Coll Cardiol . 2013;61(9):948 - 954. Duboc D, et al. Am Heart J . 2007;154(3):596 - 602. 2000 – Present Afterload Reduction With ACE Inhibitors |
Slide 107: Loss of ambulation is predictive of late physical manifestations
CO - 107 Loss of ambulation is predictive of late physical manifestations 0 5 10 15 20 25 30 Years DMD Progression is Sequential, Non - Linear and Irreversible Loss of Ambulation Death Loss of Stair Climb Early Physical Manifestations Late Physical Manifestations Ventilation Loss of Upper Limb Impai
Slide 108: Measuring DMD Progression Requires Multiple Outcome Measures
CO - 108 Measuring DMD Progression Requires Use of Multiple Outcome Measures Muscle Function • 6 - minute walk test • 4 - stair climb • 4 - stair descend • 10m walk / run Disease Progression • North Star Ambulatory Assessment (NSAA) • Loss of Ambulation Pulmonary Function • Forced vital capacity End
Slide 109: Ataluren Preserves 6MWD, TFTs, NSAA
CO - 109 Ataluren Preserves 6MWD, TFTs, NSAA and Predicts for Overall Delay in Disease Progression Dx 5 Years 9 Years 14 Years 20 Years Disease progression in DMD Loss Ambulation NSAA Functions Loss of Stair Climb Death Ventilation Loss of Upper Limb Function Adapted from Bushby , Connor. Clin Inves
Slide 110: Loss of Ambulation Predicts Subsequent Progression Milestones
CO - 110 Loss Ambulation Loss Ambulation Loss of Ambulation Predicts for Subsequent Progression Milestones Adapted from Bushby , Connor. Clin Investig ( Lond ), 2011; McDonald, et al. Muscle Nerve, 2013. Dx Death Ventilation Loss Ambulation NSAA Functions Loss of Upper Limb Function 5 Years 9 Years
Slide 111: Glucocorticoids target NF-κB Chronically Activated in DMD
Glucocorticoids target NF - κB which is Chronically Activated in DMD • miRNAs in muscle microenvironments cause variable dystrophin in muscular dystrophy • miRNAs are elevated in dystrophic myofibers and increase with disease severity • Inflammatory cytokines induce miRNAs , and antiinflammatories b
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Slide 113: CINRG Duchenne Natural History Study
CINRG - Duchenne Natural History Study: Prospective multicenter longitudinal observational study in DMD # An initial cohort of patients was recruited between 2006 and 2009 (n = 340) and a second cohort of 4 – 8 year olds between 201 2 and 2015; † Patients who provided at least one FVC assessment at
Slide 114: Clinically meaningful milestones in DMD
8 Milestones that are clinically meaningful in DMD (based on PODCI Transfer / Basic Mobility) Stand from supine < 5 sec Stand from supine 5 - 10 sec Stand from supine > 10 sec or Lost Rise from Floor Lost 4 - Stair Climb Still Amb Non - Amb Full Overhead reach Lost Full Overhead Reach (Retains hand
Slide 115: Age at Loss of Ambulation Predicts Age at Onset of 1 liter FVC
Age at Loss of Ambulation Predicts Age at Onset of 1 liter FVC (CINRG Data) FVC < 1 liter increases risk of death HR (95% CI) 4.1 (1.3, 13.1) QC (QC cjs 05Sep17) 0.00 0.25 0.50 0.75 1.00 0 10 20 30 Age (years) Proportion Reaching FVC of 1L Ambulatory patients age 9 - 18 at study entry Number at Risk
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Slide 121: Static positioning leads to contractures in DMD
Static positioning leads to contractures in DMD | Capricor, Inc. │KOL Lunch on DMD 121
Slide 122: Static positioning leads to contractures in DMD
Static positioning leads to contractures in DMD | Capricor, Inc. │KOL Lunch on DMD 122
Slide 123: Scoliosis in DMD
Scoliosis in DMD Without steroids 80 - 90% require fusion With steroids 20 - 30% require fusion | Capricor, Inc. │KOL Lunch on DMD 123
Slide 124: Quality of Life Implications for Untreated Spine Deformity
Quality of Life Implications for Untreated Spine Deformity | Capricor, Inc. │KOL Lunch on DMD 124
Slide 125: Spinal Fusion / instrumentation
Spinal Fusion / instrumentation Curve severity 20 - 40 degrees optimal FVC > 40% predicted optimal <30%FVC possible | Capricor, Inc. │KOL Lunch on DMD 125
Slide 126: Cardiomyopathy in DMD
Cardiomyopathy in DMD • Clinically significant cardiomyopathy rare before age 10; MRI changes common • Fibrosis posterior wall left ventricle • Myocardium exhibits abnormal contractility • Arrythmias • Treatment: Early ACE Inhibitors; Evidence Class Ia • enalapril , lisinopril , perindopril • ? ARBs
Slide 127: GI / Nutrition Issues
GI / Nutrition Issues • Weight Gain around time of WC • Late stage cachexia (need for G - tube/PEG) • Gut hypomotility / gastroparesis • Respiratory issues and GI procedures | Capricor, Inc. │KOL Lunch on DMD 127
Slide 128: Progression in pulmonary function loss by age
0 20 40 60 80 100 6 8 10 12 14 16 18 20 22 24 26 28 30 Age (years) Mean PFT %p (SE) FVC%p PEF%p MIP%p MEP%p Progression in pulmonary function loss by age Source: CINRG DNHS. | Capricor, Inc. │KOL Lunch on DMD 128
Slide 129: Brooke upper extremity functional grade
Brooke upper extremity functional grade 1 2 3 4 5 6 Starting with arms at the sides, the patient can abduct the arms in a full circle until they touch above the head. Can raise arms above head only be flexing the elbow or using accessory muscles. Cannot raise arms above head but can raise an 8oz. gl
Slide 130: %FVC decline by Brooke upper extremity functional grade
OHR | No OHR Hand to Mouth | No Hand to Mouth %FVC decline by Brooke upper extremity functional grade DHNS all data. Retained overhead reach Lose overhead reach Retained hand to mouth Lose hand to mouth Retained hand function No distal hand function | Capricor, Inc. │KOL Lunch on DMD 130
Slide 131: Potential for Combination Treatments in DMD
Potential for Combination Treatments in DMD ‣ Six main categories for therapeutic targets for DMD ‣ One addresses primary genetic defect; rest address downstream aspects of the pathogenesis ‣ Targeting any single pathway may be an approvable mono - therapy ‣ Future treatment paradigm may involve tar
Slide 132: Potential for Combination Treatments in DMD
Potential for Combination Treatments in DMD Increasing muscle mass and regeneration Decreasing inflammation and fibrosis Correcting perturbations in Calcium handling Mitochondria dysfunction Replacement of dystrophin/ utrophin Correcting blood flow regulation DMD Therapeutic Development ‣ NF - κB Is
Slide 133: Potential for Combination Treatments in DMD
Potential for Combination Treatments in DMD Increasing muscle mass and regeneration Decreasing inflammation and fibrosis Correcting perturbations in Calcium handling Mitochondria dysfunction Replacement of dystrophin/ utrophin Correcting blood flow regulation DMD Therapeutic Development ‣ Therapeuti
Slide 134: Summary
Summary 1. DMD natural history is changing, with significant preservation of motor, cardiac and pulmonary function, leading to increased survival over the past three decades 2. Cannot apply a single primary endpoint across the ambulatory or non - ambulatory spectrum of disease 3. Glucocorticoid use
Slide 135: Acknowledgements
Acknowledgements CINRG Investigators NICHD
Slide 136: BRAVE Program: Understanding Patient and Caregiver Preferences
BRAVE Program B enefit - R isk A ssessment V aluation & E vidence Understanding Patient and Caregiver Preferences Ryan Fischer, SVP Community Engagement Presented By: Pat Furlong | Capricor, Inc. │KOL Lunch on DMD
Slide 137: Why Collect Patient Preference Information (PPI)?
Why Collect Patient Preference Information (PPI)? What can be learned? • Identify unmet medical needs • Provide insight into symptom priorities • Identify target treat profile • Inform endpoint development • Inform development of PRO’s • Understand risk tolerance, tolerance for uncertainty, and bene
Slide 138: Stated Preference Methods
Stated Preference Methods • Methods for collecting and analyzing data about what people think and feel – Special types of surveys that provide numbers to explain how important ‘good’ things are in comparison to ‘bad’ things. – How much ‘bad’ will people accept for the ‘good’ ? | Capricor, Inc. │KOL
Slide 139: Pilot Preference Study
Pilot Preference Study Community Engaged, Patient Centric Approach Collaborator : Johns Hopkins School of Public Health (Dr. John Bridges) Research Objectives: – To understand meaningful preferences of caregivers for emerging Duchenne therapies – Demonstrate a process by which a patient advocacy org
Slide 140: Example Task
Example Task • Effect on muscle function (none, slows, stops) • Gain in expected lifespan (none, 2, 5 years) • Post - approval information (none, 1, 2 years) • Nausea (none, loss of appetite, loss of appetite and occasional vomiting) • Risk of bleeds (none, risk of bleeding gums and increased bruisi
Slide 141: Results – what we learned
Results – what we learned • Caregivers are willing to accept considerable risk in order to achieve stopping or slowing the progression of Duchenne (non curative) • Caregivers were willing to trade off on longer lifespan choosing quality of life over quantity for benefit • Caregivers prioritized the
Slide 142: Study – Pulmonary Treatment for Duchenne
Study 2 – Pulmonary Treatment for Duchenne Study Sponsor: Santhera Collaborator: Johns Hopkins School of Public Health (Dr. John Bridges) Research Objectives: Aimed to evaluate • The degree to which pulmonary outcomes represent meaningful benefit • Acceptable risk, harms, burden given the pulmonary
Slide 143: Second Study on Lung Benefits
Second Study on Lung Benefits | Capricor, Inc. │KOL Lunch on DMD 143
Slide 144: Results – what we learned
Results – what we learned • Patients and caregivers prioritized pulmonary and cardiac benefit among non skeletal treatment targets • Patients and caregivers were willing to accept risk and burden in order to achieve pulmonary benefits. • There was little difference between the preferences of patient
Slide 145: Study 4: Treatment Preferences for Duchenne: A global study
Study 4: Treatment Preferences for Duchenne: A global study (2018) Funding Support : Pfizer, Everylife Foundation Collaborator : Johns Hopkins School of Public Health (Dr. John Bridges) 6 participating countries and patient group lead: USA – PPMD UK – Duchenne UK Canada – Jesse’s Journey Netherlands
Slide 146: Experiments: Treatment Preferences and Unmet Needs
Experiments • Treatment Preferences (DCE) Unmet Needs Prioritizations • Research outcomes • Care standards • Trial eligibility • Clinical trials • No placebo • Compassionate use • Social initiatives Unmet needs A Unmet needs B Clinical trials Care standards Social initiatives No placebo Compassionat
Slide 147: Familiarity with Drug Development, clinical trials, and reimbursement
Familiarity with Drug Development clinical trials, and reimbursement Very much Somewhat A little bit Not at all Does not exist in my country How familiar are you with drug discovery and pre - clinical research in your country? ☐ ☐ ☐ ☐ ☐ How familiar are you with clinical studies in your country? ☐ ☐
Slide 148: Timeline
Timeline • Stakeholder engagement Sept 2017 - January 2018 • Survey Development Dec 2017 - February 2018 • Survey Implementation March 2018 - May 2018 • Pote ntial Wave 2 June 2018 - Oct 2018 (Europe) • Publications • Oct 2018 | Capricor, Inc. │KOL Lunch on DMD 148
Slide 149: Study 5: Duchenne Gene Transfer Preference Study
Study 5: Duchenne Gene Transfer Preference Study & Educational Initiative Qualitative Interviews Stated Preference Survey Educational Initiative Sponsors: Pfizer and Solid Biosciences Collaborator: RTI International (Holly Peay , PhD) Research Objective : Explore preferences and risk tolerance about
Slide 150: Qualitative Results – What we learned
Qualitative Results – What we learned Benefits Risks Limitations (Caveats) Respondents highly valued potential benefits to skeletal muscle, cardiac, and pulmonary function • Muscle : differently valued for quality of life impacts based on progression • Cardiac/pulmonary : greater relative importance
Slide 151: Development of Survey
Development of Survey (Quantitative data) Anticipated recruitment numbers – 150 parents and 50 adults with Duchenne Inclusion Criteria • Adults with Duchenne muscular dystrophy (must be at least 18 years old) • The parent of a person with Duchenne muscular dystrophy, or a guardian (current or past)
Slide 152: Whiteboard video about Gene Therapy before survey
Participants are required to view a 2 minute whiteboard video about Gene Therapy before taking survey | Capricor, Inc. │KOL Lunch on DMD 152
Slide 153: Threshold Experiment (approved therapy)
Threshold Experiment (approved therapy) • Imagine that your child’s doctor offers your child gene therapy for Duchenne. The doctor shows you these two graphs. They show the average benefit experienced by 2,000 people who used gene therapy. The solid lines show how using gene therapy has helped their
Slide 154: Risk of gene therapy
Your doctor tells you about the risk of gene therapy. 1 out of 2,000 people with Duchenne will die from using gene therapy. The person will die within a week after using it. The other 1,999 people will not die from gene therapy. Would you choose gene therapy? Risk Numbers: 1/2000 10/2000 20/2000 200
Slide 155: Best Worst Experiment (clinical trial)
Best Worst Experiment (clinical trial) Clinical Trial Attributes • Chance of improved muscle function • Chance of improved heart function • Chance of improved lung function • Benefit lasts 10 years • Trial uses placebo group • Lowest dose may be too low for benefit • Not eligible for future trials •
Slide 156: Task Example
Which is most important to your decision about whether to join the trial? What is least important to your decision? Task Example Most important to my decision Least important to my decision | Capricor, Inc. │KOL Lunch on DMD 156
Slide 157: Timeline
Timeline • Qualitative study - completed • Draft survey - completed • Recruitment – January 2018 – March 2018 • Analysis – early spring • Report - late spring | Capricor, Inc. │KOL Lunch on DMD 157
Slide 158: Thank you!
Thank you! | Capricor, Inc. │KOL Lunch on DMD
Slide 159: HOPE-2 Trial Design
│ Capricor , Inc. │KOL Lunch on DMD HOPE - 2 Trial Design Presented By: Deborah Ascheim M.D.
Slide 160: HOPE-2 Trial
│ Capricor , Inc. │KOL Lunch on DMD HOPE - 2 Trial S C R E E N I N G R A N D O M I Z E CAP - 1002, N=42 150M CDCs IV infusion q3m Placebo, N=42 IV infusion q3m 1:1 Dose #1 M3 M6 M9 M12 D1 W4 • Randomized, double - blind, placebo - controlled trial • N ≤ 84 • Total of 4 doses of IV CAP - 1002 or plac
Slide 161: Endpoints
│ Capricor , Inc. │KOL Lunch on DMD Primary • Upper - limb function at Month 12 by mid - level PUL • Pre - specified safety events Endpoints Secondary • Upper - limb function (mid - level PUL) at Months 3, 6, & 9 • Cardiac function by MRI • Incidence and severity of AEs Exploratory • Elbow, grip, &
Slide 162: HOPE-2 Considerations
│ Capricor , Inc. │KOL Lunch on DMD • Ambulatory and non - ambulatory boys and young men with compromised upper limb function considered for enrollment • Later stage disease few competitors • We believe CAP - 1002 is complementary to other disease modifying therapies (dystrophin modulating Rxs ) HOP
Slide 163: DMD Advisory Board Collaborators
│ Capricor , Inc. │KOL Lunch on DMD • HOPE - 1 trial patients • Patient advocacy group partners DMD Advisory Board Collaborators - Barry Byrne, MD, PhD - John Jefferies, MD - Michael Taylor, MD PhD - Michelle Eagle, PhD - Oscar Henry Mayer, MD - Ron Victor, MD - Richard Finkel, MD - Craig McDonald,
Slide 164: Thank you Q&A
│ Capricor , Inc. │KOL Lunch on DMD Thank you Q&A
Capricor Therapeutics — Technical Presentation (March 2018) on 6ix