Abeona Therapeutics Inc. · NASDAQ:ABEO
Abeona Therapeutics — Investor Day (December 2018)
105 slides from Abeona Therapeutics's investor day presentation, Dec 6, 2018
Slide 1: Abeona Therapeutics 2018 R&D Day
Abeona Therapeutics 2018 R&D Day MONSIE Living with RDEB 2018 R&D Day December 6, 2018
Slide 2: R&D Day agenda
Abeona Therapeutics 2018 R&D Day 8:00 Breakfast / Registration 8:45 “The Edge of Hope” and Opening Remarks 9:00 EB - 101 Review: Pivotal Phase 3 Preparation Jean Tang, M.D., Ph.D., Jay Bircher, Max Colao, João Siffert, M.D. 9:30 Panel: CMC and Regulatory: Challenges, Strategies, and Capabilities Kay
Slide 3: EB-101 for Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Abeona Therapeutics 2018 R&D Day NOEMI Living with RDEB EB - 101 for Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Slide 4: EB-101: Breakthrough Therapy for RDEB
Abeona Therapeutics 2018 R&D Day EB - 101: Breakthrough Therapy for RDEB Jean Tang, M.D., Ph.D. Clinical Overview and Phase 1/2 Trial Results Jay Bircher EB - 101 Manufacturing and Quality Update Max Colao EB Commercial Assessment João Siffert, M.D. Abeona Clinical Program Update Source: Ari Espay 4
Slide 5: Type VII collagen gene anchors epidermis to dermis
Abeona Therapeutics 2018 R&D Day Type VII collagen (C7) gene is responsible for anchoring the epidermis to dermis RDEB RDEB is among the most devastating forms of EB, caused by mutation of type VII collagen and breakdown of anchoring fibrils Healthy Skin RDEB Skin 5
Slide 6: RDEB clinical manifestations
Abeona Therapeutics 2018 R&D Day Dermatologic • Widespread blistering and extensive dystrophic scarring • Born without patches of skin • Infections from open wounds or blisters • 75 - 90% lifetime risk of squamous cell carcinoma Oral Cavity / GI • Fusion of tongue to floor of month ( ankyloglossia )
Slide 7: No approved treatments; wound care is costly
Abeona Therapeutics 2018 R&D Day No approved treatments – wound care is essential to promote healing & prevent fluid loss, but time - consuming, painful, & costly Standard Blister and Wound Dressing • Dressings typically consist of three layers • Direct costs associated with RDEB wound care range fr
Slide 8: EB-101: Ex-Vivo Autologous Gene-Corrected Cell Therapy
Abeona Therapeutics 2018 R&D Day EB - 101: Ex - Vivo Autologous Gene - Corrected Cell Therapy EB - 101: 26 - days post growth EB - 101: ready for patients 8
Slide 9: EB-101 retroviral vector transduction efficiency
Abeona Therapeutics 2018 R&D Day 0 0.5 1.0 1.5 3 4 1 2 3 4 1 2 60 65 70 75 80 85 Virus Transduction Efficiency, % EB - 101: Retroviral Vector LZRSE with 9 kB COL7A1 Gene Virus Transduction Efficiency and Mean Proviral Copy Number per Cell in Corrected Keratinocytes in 4 Patients With RDEB Virus tran
Slide 10: Natural History study supports clinical design
Abeona Therapeutics 2018 R&D Day 128 - patient Natural History study supports clinical design Multi - year enrollment complete: • 1,436 wounds (1,041 recurrent wounds/395 chronic open wounds) • 100% of patients reported chronic open wounds (no healing> 3m) or recurrent wounds • 38% of chronic open w
Slide 11: EB-101 Phase 1/2 Trial Results
Abeona Therapeutics 2018 R&D Day EB - 101: Phase 1/2 Trial Results Primary Endpoint: Safety • Wound healing percent versus baseline at 3, 6 and 12 months Secondary Endpoints • Duration of Type VII collagen (C7) expression • Presence of anchoring fibrils • Patient Reported Outcomes: Pain, Itch and Du
Slide 12: Phase 1/2 Trial Patient Characteristics
Abeona Therapeutics 2018 R&D Day EB - 101: Phase 1/2 Trial Patient Characteristics Patient # 1 2 3 4 5 6 7 Age 23 19 32 18 32 32 45 Sex M M M M F M F COL7A1 Mutation 1 (Location) delC exon delC exon dupC ( exon C> T exon dupC ( exon C> T exon
Slide 13: Primary endpoint safety and wound healing
Abeona Therapeutics 2018 R&D Day Primary endpoint (safety): No systemic viral infection, immune reaction, or squamous cell carcinoma Chronic wounds >5 yr Healed wounds (6 months) 13
Slide 14: Gene therapy skin grafts restore collagen 7
Abeona Therapeutics 2018 R&D Day Site Location Descript Estimated duration 3m 6m 12m A R lateral hand Erosion 3 - 5 yrs B R medial hand Scar tissue 3 - 5 yrs C L ventral foot Erosion and scar 3 - 5 yrs D L hand Scar tissue 3 - 5 yrs E R foot Erosion and scar 3 - 5 yrs Z L ventral foot Induced wound
Slide 15: Patient 5: Wound healing
Abeona Therapeutics 2018 R&D Day Patient 5: Wound healing (left arm, chronic open wound (10+yr) Baseline Grafting 9 months A B A B 15
Slide 16: Patient 5: Wound healing over time
Abeona Therapeutics 2018 R&D Day C D F E Patient 5: Wound healing seen for 9 - 12 months C D Baseline Grafting 9 months 16
Slide 17: Wound-level results by patient
Abeona Therapeutics 2018 R&D Day 2 years 5 years A R distal forearm Erosion >5 yrs B L forearm Erosion >5 yrs C R proximal forearm Erosion >5 yrs D R shoulder Inflamed erosion >5 yrs E L arm New blister 1 wk Z R arm Induced wound New A Central chest Erosion >5 yrs B L shoulder Erosion and scar >5 yr
Slide 18: EB-101 improved patient-reported outcomes
Abeona Therapeutics 2018 R&D Day EB - 101 significantly improved patient - reported outcomes Pre - Grafting 3 Month 6 Month 9 Month 12 Month Presence of PAIN at wound site (% reported yes) 58% 0% 17% 20% 0% ITCH at wound site (% reported yes) 67% 5% 17% 50% 25% Lack of durability at wound site (% re
Slide 19: Summary of Phase 1/2 Trial Results
Abeona Therapeutics 2018 R&D Day Summary of Phase 1/2 Trial Results • Focus on large, difficult to treat chronic wounds • No product - related serious adverse events observed to date • Significant and durable wound healing, with up to 5 years of follow - up • Continuous type VII collagen expression
Slide 20: The Elisa Linton Center for Rare Disease Therapies Manufacturing
Abeona Therapeutics 2018 R&D Day The Elisa Linton Center for Rare Disease Therapies Manufacturing
Slide 21: Facilities/Production – Elisa Linton Center
Abeona Therapeutics 2018 R&D Day Facilities/Production – Elisa Linton Center • Upfront investment to establish GMP and preparation for commercial production in Cleveland strengthens ability to execute product launch • Established GMP manufacturing of EB - 101 gene - corrected cell therapy ⎻ Cell Pro
Slide 22: Abeona Therapeutics 2018 R&D Day 22
Abeona Therapeutics 2018 R&D Day 22
Slide 23: Commercialization
Abeona Therapeutics 2018 R&D Day MONSIE Living with RDEB Commercialization
Slide 24: EB-101: Transformative treatment for RDEB patients
Abeona Therapeutics 2018 R&D Day First in Class Therapy • No approved RDEB treatments • EB - 101 restores normal type VII collagen expression and skin function Differentiated MOA • Autologous, gene - corrected cell therapy • Normal COL7A1 gene is inserted into a patient’s own skin cells (keratinocyt
Slide 25: EB-101 Summary and Next Steps
Abeona Therapeutics 2018 R&D Day EB - 101 Summary and Next Steps Successful Phase 1/2 • Favorable safety profile with no product - related SAEs to date • Significant and durable wound healing, with up to 5 years of follow - up Established GMP manufacturing capability at Abeona • Manufacture both cli
Slide 26: VITAL: Pivotal Phase 3 Trial Design
Abeona Therapeutics 2018 R&D Day VITAL: A Pi v otal Phase 3 Tr i al S t udy of EB - 101 for the Tre a tment of Recessive Dystrophic Epidermo l ysis Bullosa (RDEB) • Multicenter, n=10 - 15 evaluable pts (≥35 grafts), randomized (up to 6 wounds >20 cm 2 wounds unhealed for at least 6 months per patien
Slide 27: CMC and Regulatory Landscape for Gene Therapy
Abeona Therapeutics 2018 R&D Day Maritza McIntyre, Ph.D. CMC and Regulatory Landscape for Gene Therapy: Challenges, Capabilities & Strategies
Slide 28: Gene Therapy Landscape: CMC Opportunities and Challenges
Abeona Therapeutics 2018 R&D Day Gene Therapy Landscape: CMC Opportunities and Challenges • The gene therapy field has advanced to offer the potential for effective cures or significant improvements in the lives of patients with rare diseases and cancer • Early, robust efficacy is often demonstrated
Slide 29: Gene Therapy Landscape: CMC Opportunities and Challenges
Abeona Therapeutics 2018 R&D Day Gene Therapy Landscape: CMC Opportunities and Challenges • Majority of translational/early clinical gene therapy research conducted by academic researchers and/or startups spun out of academia ⎻ Lack of regulatory and product development expertise to map out lifecycl
Slide 30: Gene Therapy Landscape: CMC Opportunities and Challenges
Abeona Therapeutics 2018 R&D Day Gene Therapy Landscape: CMC Opportunities and Challenges • Paradigm shifts in gene therapy CMC ⎻ Draft FDA Guidance on Gene Therapy for Rare Diseases (July 2018) recommends advancing CMC development to have more elements in place prior to first - in - human studies ⎻
Slide 31: Fireside Chat: Gene Therapy in 2019 – What's Next?
Abeona Therapeutics 2018 R&D Day Barry Byrne, M.D., Ph.D. Tim Miller, Ph.D. Fireside Chat: Gene Therapy in 2019 – What’s Next?
Slide 32: MPS III Programs
Abeona Therapeutics 2018 R&D Day BREA Living with Sanfilippo syndrome type A MPS III Programs
Slide 33: Sanfilippo Syndrome (MPS IIIA and IIIB)
Abeona Therapeutics 2018 R&D Day Cell with lysosome dysfunction & accumulation of enzyme substrate Normal cell Sanfilippo Syndrome (MPS IIIA and IIIB) Inherited monogenic disorders causing lysosomal enzyme deficiency • Two most common forms categorized by deficient enzymes: - MPS IIIA ( SGSH ), MPS
Slide 34: Natural History: Comparator control arm
Abeona Therapeutics 2018 R&D Day Natural History: Comparator control arm to assess treatment effects
Slide 35: Prospective one-year Natural History study
Abeona Therapeutics 2018 R&D Day Enrollment complete : 25 subjects, 15 MPS IIIA & 10 MPS IIIB • Study visits : Baseline, 6 and 12 months • Neurocognitive and behavioral rating assessments - Timed functional motor tests - Standard laboratory assessments - Serum/leukocyte NAGLU or SGSH activity - Qual
Slide 36: Mullen Developmental Age: Natural History Study
Abeona Therapeutics 2018 R&D Day Mullen Developmental Age: Nationwide Children’s Hospital Natural History Study 0 3 6 9 1 2 1 5 1 8 2 1 2 4 2 7 3 0 3 3 3 6 3 9 4 2 4 5 4 8 5 1 5 4 5 7 6 0 6 3 6 6 6 9 7 2 7 5 7 8 8 1 8 4 8 7 9 0 9 3 9 6 9 9 1 0 2 1 0 5 1 0 8 1 1 1 1 1 4 1 1 7 0 3 6 9 12 15 18 21 24 2
Slide 37: MPS IIIA Natural History: Cognitive Assessments
Abeona Therapeutics 2018 R&D Day Chronological Age (mo) MPS IIIA Natural History: Cognitive Assessments (N=25) 36m Cognitive Age Equivalent (mo) Rapid Progressors Slow Progressors Shapiro et al. 2016 37
Slide 38: MPS IIIA Natural History: Cognitive Developmental Age
Abeona Therapeutics 2018 R&D Day MPS IIIA Natural History: Cognitive Developmental Age (N=46) Calendar Age (yr) Developmental Age (yr) University of Pittsburgh - Buhrman et al. 2013 38
Slide 39: ABO-102 Clinical Trial Update
Abeona Therapeutics 2018 R&D Day ABT - 001 Clinical Trial Update
Slide 40: Phase 1/2 Clinical Trial (AAV9-SGSH) for MPS IIIA
Abeona Therapeutics 2018 R&D Day A Phase 1/2 Clinical Trial (AAV9 - SGSH) for MPS IIIA Intravenous Dosing • Cohort 1 : 5 x 10 12 vg/kg (n=3) • Cohort 2 : 1 x 10 13 vg/kg (n=3) • Cohort 3 : 3 x 10 13 vg/kg (9 - 12) 8 subjects treated Primary Endpoint • Safety Secondary Endpoints • Cerebrospinal Fluid
Slide 41: Current Enrollment and Follow up
Abeona Therapeutics 2018 R&D Day Age 1y7m. 4y9m. 4y5m. 2y3m. 6y5m. 5y2m. 3y2m. 2y9m. 2y5m. 5y4m. 7y0m. 1y0m. 8y0m. 3y5m. Current Enrollment and Follow up: Days Post - Injection 0.00 30.00 60.00 90.00 120.00 150.00 180.00 210.00 240.00 270.00 300.00 330.00 360.00 390.00 420.00 450.00 480.00 510.00 54
Slide 42: Reductions in CSF Heparan Sulfate
Abeona Therapeutics 2018 R&D Day Reductions in CSF Heparan Sulfate LLQ ABT - 001 Age (mo) 0.60 0.55 0.50 0.45 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.00 CSF - HS (nmol/mL) 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 0 Cohort 1 Cohort 2 Cohort 3 42
Slide 43: Reductions in Urine Heparan Sulfate
Abeona Therapeutics 2018 R&D Day 2.75 2.50 2.25 2.00 1.75 1.50 1.25 1.00 0.75 0.50 0.25 0.00 Reductions in Urine Heparan Sulfate Age (mo) nmol/mmol creatinine 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 0 Cohort 1 Cohort 2 Cohort 3 43
Slide 44: Reductions in Liver Volumes
Abeona Therapeutics 2018 R&D Day 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.00 0.0 Reductions in Liver Volumes Normal Liver Volume Age (mo) Multiples of normal liver volume 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 0 Cohort 1 Cohort 2 Cohort 3 44
Slide 45: Mullen Developmental Age: ABO-102 vs. NHS
Abeona Therapeutics 2018 R&D Day 0369 1 2 1 5 1 8 2 1 2 4 2 7 3 0 3 3 3 6 3 9 4 2 4 5 4 8 5 1 5 4 5 7 6 0 6 3 6 6 6 9 7 2 7 5 7 8 8 1 8 4 8 7 9 0 9 3 9 6 9 9 1 0 2 1 0 5 1 0 8 1 1 1 1 1 4 1 1 7 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Mullen Dev Age ABT-001vs NHS Chronological Age (Month) D e v e
Slide 46: Mullen Developmental Age: ABO-102 vs. NHS
Abeona Therapeutics 2018 R&D Day 45 42 39 36 33 30 27 24 21 18 15 12 9 6 3 0 0369 1 2 1 5 1 8 2 1 2 4 2 7 3 0 3 3 3 6 3 9 4 2 4 5 4 8 5 1 5 4 5 7 6 0 6 3 6 6 6 9 7 2 7 5 7 8 8 1 8 4 8 7 9 0 9 3 9 6 9 9 1 0 2 1 0 5 1 0 8 1 1 1 1 1 4 1 1 7 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Mullen Dev Age ABT
Slide 47: Global Regulatory Guidance Supportive of Development Program
Abeona Therapeutics 2018 R&D Day Global Regulatory Guidance Supportive of Development Program Clinical • Acknowledged substantial reduction in disease biomarkers • Evidence of neurological improvements continued to be demonstrated • Natural History Comparator Control may be acceptable, which we may
Slide 48: Summary of MPS IIIA ABO-102 Phase 1/2 Study Data
Abeona Therapeutics 2018 R&D Day Summary of MPS IIIA ABO - 102 Phase 1/2 Study Data • N=14 as of November 2018 - Length of follow up in cohort 3: 6 months (N=6 of 8 total), 12 months (N=3 of 8 total) • Clear dose - response, and sustained improvement in biomarkers (HS CSF, Liver Volume) • Encouragin
Slide 49: Next Steps
Abeona Therapeutics 2018 R&D Day Next Steps • Amend protocol criteria in ABT - 001 Phase 1/2 study to exclusively enroll patients with greater neurological reserve (younger, higher functioning) • Continued enrollment in the MPS IIIA program • Older/lower functioning eligible patients may participate
Slide 50: MPS IIIB: ABO-101 Study Update
Abeona Therapeutics 2018 R&D Day AUSTIN Living with Sanfilippo syndrome type B MPS IIIB: ABT - 002 Study Update
Slide 51: Phase 1/2 Clinical Trial (AAV-NAGLU) for MPS IIIB
Abeona Therapeutics 2018 R&D Day 2 - year, Open - label, dose - escalation global clinical trial A Phase 1/2 Clinical Trial (AAV - NAGLU) for MPS IIIB Intravenous Dosing • Cohort 1 : 2 x 10 13 vg/kg (n=3 subjects) 1 patient treated (4.2 y/o) and 1 patient enrolled • Cohort 2 : 5 x 10 13 vg/kg (n=3 -
Slide 52: Reductions in CSF and Urine Heparan Sulfate
Abeona Therapeutics 2018 R&D Day Reductions in CSF and Urine Heparan Sulfate Age (mo) 46 49 52 55 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 0.80 0.75 0.70 0.65 0.60 0.55 0.50 0.45 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.00 Urine - HS (pmol/mmolCre) CSF - HS (pmol/mL) 52
Slide 53: Reduction in Liver Volume vs. Natural History
Abeona Therapeutics 2018 R&D Day 3.00 2.75 2.50 2.25 2.00 1.75 1.50 1.25 1.00 0.75 Reduction in Liver Volume ABT - 002 vs. Natural History Age (mo) Multiples of normal liver volume 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 114 120 126 132 138 144 53
Slide 54: Developmental Age vs. Natural History
Abeona Therapeutics 2018 R&D Day Developmental Age vs. Natural History 48 42 36 30 24 18 12 6 0 Age (mo) Cognitive Dev Age (mo) 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 114 120 126 132 138 144 Truxal et al. 2016; Whitley et al. 2018 54
Slide 55: MPS IIIB Next Steps
Abeona Therapeutics 2018 R&D Day MPS IIIB Next Steps Additional sites are being activated to increase the rate of enrollment • US, Germany, France, and the U.K. Pre - screening Protocol • Will help provide more access to screening for pre - existing antibodies against AAV9 55
Slide 56: AAV GMP Manufacturing
Abeona Therapeutics 2018 R&D Day AAV GMP MANUFACTURING
Slide 57: Elisa Linton Center: GMP Manufacturing of AAV Products
Abeona Therapeutics 2018 R&D Day Elisa Linton Center: GMP Manufacturing of AAV Products • FDA Division of Manufacturing and Product Quality (DMPQ) supports clinical or single use commercial facility • AAV Processing Facility: • Separate Upstream and Downstream Suites • Capable of Clinical and Commer
Slide 58: GMP AAV Manufacturing Facility Supportive of Clinical Translation
Abeona Therapeutics 2018 R&D Day Abeona GMP AAV Manufacturing Facility Supportive of Clinical Translation Hyperstacks 18,000 cm 2 Eppendorf Bioblu Scalable to 40L CellSTACKS 6,320 cm 2 iCellis Nano 40,000 cm 2 x 46 Staff Members x Seasoned Process Experts x Strong Management Team x Prior Manufacturi
Slide 59: ABO-202: Inspiring Hope for Patients with Infantile Batten Disease
Abeona Therapeutics 2018 R&D Day Leighton Living with CLN1 ABO - 202 Inspiring Hope for Patients with Infantile Batten Disease (CLN1)
Slide 60: ABO-202: scAAV9 for Infantile Batten Disease (CLN1)
Abeona Therapeutics 2018 R&D Day ABO - 202: scAAV9 for Treatment of Infantile Batten Disease – CLN1 • Infantile Neuronal Ceroid Lipofuscinosis (INCL) • Exclusive, worldwide license secured for AAV9 for treatment of CLN1 • Severe neurodegenerative lysosomal storage disease, currently with no approved
Slide 61: Therapeutic Approach: Combination IV and IT dosing
Abeona Therapeutics 2018 R&D Day Therapeutic Approach: Combination intravenous & intrathecal dosing • Demonstrated efficacy in CLN1 mice support rationale for clinical dosing by both intrathecal (IT) and intravenous (IV) simultaneously ⎻ IT: Intrathecal (lumbar puncture) ⎻ IV: Intravenous (tail vein
Slide 62: ABO-202: IND-Enabling Efficacy Study Designs
Abeona Therapeutics 2018 R&D Day 6 months* (26 weeks) • LD • HD 8 months Premature death 3 months* (12 weeks) • HD 1 month* (4 weeks) • LD • MD • HD 1 week* • LD • HD Birth 4.5 months* (20 weeks) ✽ IV HD ✾ IT+IV ✾ LD+LD ✾ LD+MD ✾ LD+HD ✾ HD+HD pre - symptomatic early - symptomatic symptomatic ✾ IT+I
Slide 63: Intrathecal delivery yields supraphysiological PPT1 activity
Abeona Therapeutics 2018 R&D Day Nmol/hr/mL 10 5 ≤10 0 10 4 10 3 10 2 10 1 Untreated KO WT Het ABO - 202 intrathecal delivery results in supraphysiological PPT1 activity levels in serum CLN1 mice Sustained supraphysiological levels of active PPT1 in CLN1 treated at 20 weeks of age compared to wild t
Slide 64: Intrathecal administration requires high dose for efficacy
Abeona Therapeutics 2018 R&D Day 0 3 6 9 12 15 18 21 24 27 0 25 50 75 100 KO.UNTREATED 20WK.IT-L 20WK.IT-H 26WK.IT-H 26WK.IT-L 0 3 6 9 12 15 18 21 24 27 0 25 50 75 100 KO.UNTREATED 20WK.IT-L 20WK.IT-H 20WK.IV.H 20WK.IT-L.IV-L 20WK.IT-L.IV-M 20WK.IT-L.IV-H 20WK.IT-H.IV-H 26WK.IT-H 26WK.IT-L 0 3 6 9 1
Slide 65: Intravenous administration similar to high dose IT
Abeona Therapeutics 2018 R&D Day 100 0 75 50 25 Percent survival 0 3 6 9 12 15 18 21 24 27 0 25 50 75 100 KO.UNTREATED 20WK.IT-L 20WK.IT-H 20WK.IV.H 26WK.IT-H 26WK.IT-L Intravenous ABO - 202 administration in 20 - week old symptomatic mice is similar to high dose IT Age (mo) 0 27 9 15 21 24 3 6 12 1
Slide 66: Combination dosing improves survival
Abeona Therapeutics 2018 R&D Day 0 3 6 9 12 15 18 21 24 27 0 25 50 75 100 KO.UNTREATED 20WK.IT-L 20WK.IT-H 20WK.IV.H 20WK.IT-L.IV-L 20WK.IT-L.IV-M 20WK.IT-L.IV-H 20WK.IT-H.IV-H 26WK.IT-H 26WK.IT-L 100 0 75 50 25 Percent survival Age (mo) 0 27 9 15 21 24 3 6 12 18 0 3 6 9 121518212427 0 25 50 75 100
Slide 67: Intrathecal administration improves motor function
Abeona Therapeutics 2018 R&D Day 0 3 6 9 12 15 0 10 20 30 40 50 60 ! ! ! ! ! ! ! ! ! ! ! ! ! ! Untreated Het Untreated KO 20WK.IV-M.IT-L ! 20WK.IV-L.IT-L ! 20WK.IT.H 20WK.IV-H 20WK.IV-H.IT-L ! 20WK.IV-H.IT-H ! 26WK.IT.H 0 3 6 9 12 15 0 100 200 300 26WK.IT.H 20WK.IT.H Untreated KO Untreated Het 0 300
Slide 68: Intravenous administration improves motor function
Abeona Therapeutics 2018 R&D Day 0 300 200 100 Latency to fall (secs) Age (mo) 0 15 9 12 3 6 0 3 6 9 12 15 0 100 200 300 26WK.IT.H 20WK.IV-H 20WK.IT.H Untreated KO Untreated Het 0 3 6 9 12 15 0 10 20 30 40 50 60 ! ! ! ! ! ! ! ! ! ! ! ! ! ! Untreated Het Untreated KO 20WK.IV-M.IT-L ! 20WK.IV-L.IT-L !
Slide 69: Combination dosing improves motor function (rotarod)
Abeona Therapeutics 2018 R&D Day 0 300 200 100 Latency to fall (secs) 0 15 9 12 3 6 0 3 6 9 12 15 0 100 200 300 ! ! ! ! ! ! ! ! ! ! ! ! ! ! 20WK.IV-H.IT-H ! 26WK.IT.H 20WK.IV-L.IT-L ! 20WK.IV-M.IT-L ! 20WK.IV-H.IT-L ! 20WK.IV-H 20WK.IT.H Untreated KO Untreated Het 0 3 6 9 12 15 0 10 20 30 40 50 60 !
Slide 70: Combination dosing improves motor function (wire hang)
Abeona Therapeutics 2018 R&D Day 40 0 30 20 10 50 60 0 3 6 9 12 15 0 10 20 30 40 50 60 Untreated Het Untreated KO 20WK.IT.H 26WK.IT.H 0 3 6 9 12 15 0 10 20 30 40 50 60 ! ! ! ! ! ! ! ! ! ! ! ! ! ! Untreated Het Untreated KO 20WK.IV-M.IT-L ! 20WK.IV-L.IT-L ! 20WK.IT.H 20WK.IV-H 20WK.IV-H.IT-L ! 20WK.I
Slide 71: Combination dosing improves motor function (wire hang)
Abeona Therapeutics 2018 R&D Day 40 0 30 20 10 50 60 0 3 6 9 12 15 0 10 20 30 40 50 60 ! ! ! ! ! ! ! ! ! ! ! ! ! ! Untreated Het Untreated KO 20WK.IV-M.IT-L ! 20WK.IV-L.IT-L ! 20WK.IT.H 20WK.IV-H 20WK.IV-H.IT-L ! 20WK.IV-H.IT-H ! 26WK.IT.H 0 3 6 9 12 15 0 10 20 30 40 50 60 ! ! ! ! ! ! ! ! ! ! ! ! !
Slide 72: Combination dosing improves cognition and learning
Abeona Therapeutics 2018 R&D Day 0 3 6 9 12 15 0 5 10 15 20 25 ! ! ! ! ! ! ! Untreated Het Untreated KO 20WK.IT.H 20WK.IV-H 20WK.IV-H.IT-L ! 20WK.IV-M.IT-L ! 20WK.IV-L.IT-L ! 20WK.IV-H.IT-H ! 0 3 6 9 12 15 0 5 10 15 20 25 ! ! ! ! ! ! ! Untreated Het Untreated KO 20WK.IT.H 20WK.IV-H 20WK.IV-H.IT-L !
Slide 73: ABO-202: Phase 1/2 Clinical Trial
Abeona Therapeutics 2018 R&D Day ABO - 202: Phase 1/2 Clinical Trial • IND - enabling toxicology studies completed ⎻ Strong safety, with no significant toxicology findings in the combination dose escalation study • IND - enabling efficacy studies demonstrate normalized survival, muscle function and
Slide 74: Building New Futures for Patients with Juvenile Batten Disease (CLN3)
Abeona Therapeutics 2018 R&D Day Theo Living with CLN3 Building New Futures for Patients with Juvenile Batten Disease (CLN3)
Slide 75: scAAV9 for Juvenile Batten Disease (CLN3)
Abeona Therapeutics 2018 R&D Day scAAV9 for the treatment of Juvenile Batten Disease (CLN3) • Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) • Exclusive, Worldwide License secured for AAV9 for treatment of CLN3 • Caused by Autosomal recessive (inherited) mutation in the CLN3 gene ⎻ Initially present
Slide 76: Proof of concept studies in CLN3 mice
Abeona Therapeutics 2018 R&D Day scAAV9 for the treatment of Juvenile Batten Disease (CLN3) Proof of concept studies: scAAV9 treated CLN3 Mice Improved muscle function 3 Months Post - Injection Preclinical summary: • Multi - year POC studies from Univ. Nebraska Medical Center • Intravenous delivery
Slide 77: IV scAAV9.CLN3 biodistribution into the CNS
Abeona Therapeutics 2018 R&D Day Intravenous delivery of scAAV9.CLN3 results in significant, dose - dependent biodistribution into the CNS and peripheral organs in ADULT CLN3 mice Adult mice assessed 1 month post ABO - 202 administration Control scAAV9.CLN3 Brain Eye Cervical Spine Copies per 1ug gD
Slide 78: scAAV9.CLN3 biopotency and efficacy
Abeona Therapeutics 2018 R&D Day Intravenous delivery of scAAV9.CLN3 – biopotency and efficacy Cytosol Membrane Cytosol Membrane Cytosol Membrane Vehicle Male Female Restored expression in peripheral tissues one month post - injection in CLN3 mice scAAV9.CLN3 treated Males Females Unaffected wt mice
Slide 79: 2019 Batten Disease Clinical Trials: World Leading NCL Centers
Abeona Therapeutics 2018 R&D Day 2019 Batten Disease Clinical Trials: World Leading NCL Centers and Natural History Experts • Combined >15 years of Batten Disease Natural History Study Principal Investigators • Subject matter experts on Batten disease manifestations, neurological assessments and cli
Slide 80: Next Generation AIM AAV Platform
Abeona Therapeutics 2018 R&D Day Next Generation AIM TM AAV Platform
Slide 81: AIM Vector Platform
Abeona Therapeutics 2018 R&D Day AIM™ Vector Platform • AAV viral vector platform selected to target CNS, lung, skin, muscle, liver and other tissues • Initial library of 64 first generation novel AAV Capsids Key Advantages of AIM™ • First generation demonstrated increased gene delivery efficiency t
Slide 82: Improving Second and Third Generation AIM AAV Capsids
Abeona Therapeutics 2018 R&D Day Improving Second and Third Generation of AIM TM AAV Capsids AAV Variable Region: I II III I V V VI VII VIII XI Version 102 Version 102_214 Version 102_3 Version 102_4 Version 102_5 Version 102_6 Version 102_7 Match AAV 102 Match naturally - occurring serotypes Capsid
Slide 83: AIM Capsid enhanced tissue tropism after IV administration
Abeona Therapeutics 2018 R&D Day Case Study: AIM TM Capsid enhanced tissue tropism for AAV after intravenous administration AAV - 102 # First Generation AIM TM 4.6 fold AAV - 102 # Third Gen ~500 fold AAV - 102 Second Gen 47 fold # C o n t r o l p I T B 1 0 2 * p I T 1 1 0 - 1 0 2 p I T B 1 0 2 _ 2
Slide 84: Third generation AAV214 crosses blood-brain barrier
Abeona Therapeutics 2018 R&D Day Case Study: Third generation intravenous delivery of AAV214 crosses blood - brain - barrier in mice 0 50 100 150 200 250 300 Brain Eyes Heart Lungs Spleen Kidneys Testis Muscle S. Nerve C. Cord L. Cord Liver AAV9 IN VIVO IV DELIVERY IN MICE Compared to AAV9, % 1600 1
Slide 85: Intrathecal delivery of AAV204 into Non-Human Primates
Abeona Therapeutics 2018 R&D Day Intrathecal delivery of AAV204 into Non - Human Primates: Penetrating the CNS 1 10 100 1,000 10,000 100,000 1,000,000 10,000,000 Copies per 50 ng RNA AAV9 AAV204 -RT Mean + SDx4 -RT Mean + SDx2 • Intrathecal delivery • 30 Days post dosing • Same promoter • 10 - 100 f
Slide 86: AAV204 Escapes AAV9 Neutralizing Antibodies
Abeona Therapeutics 2018 R&D Day Light Neutralizing Antibody Assay: • AAV9 or AAV204 mixed with serum from AAV9 treated subject • Added onto cells in culture (MOI 2.5E5) • Readout of light emitted from the cells AAV INFECTION No Light AB AGAINST AAV NO INFECTION (AAV BINDING IS “NEUTRALIZED”) AAV204
Slide 87: AIM AAV-204: Delivering Genes that Target Eye Disorders
Abeona Therapeutics 2018 R&D Day AIM TM AAV - 204: A Tool for Delivering Genes that Target Eye Disorders • Multiple Routes of Administration • ABO - 50X Product Pipeline: Studies in Non - Human Primates 87
Slide 88: AIM: Expanding the Gene Therapy Toolbox for Eye Disorders
Abeona Therapeutics 2018 R&D Day AIM TM : Expanding the Gene Therapy Toolbox for Eye Disorders Ref: Khabou et al.2016 : Mechanisms of Enhanced Transduction by AAV2 - 7m8, Willett, Front. Immunol.,2013 • The Eye is immune privileged tissue • Very small amounts of virus necessary for therapeutic benef
Slide 89: Inherited Retinal Dystrophies Affect Photoreceptors and RPE
Abeona Therapeutics 2018 R&D Day 80% of Inherited Retinal Dystrophies Affect Photoreceptors & Retinal Pigmented Epithelial Layers Diseases affecting photoreceptor and RPE cells • RP (rec., dom. and X - linked) • BEST • LCA • CRD • Stargardt’s • Choroideremia • Usher Syndrome • Achromatopsia 89
Slide 90: AIM for the Eye: Subretinal vs. Intravitreal
Abeona Therapeutics 2018 R&D Day AIM TM for the Eye: Enabling Gene Therapy Delivery for Ophthalmology Diseases Subretinal Intravitreal Pros Direct contact between vector and target cells Injection can be performed at any out - patient eye clinic FDA - approved route of AAV administration ( Luxturna
Slide 91: AIM Capsids Demonstrate Enhanced Delivery to the Eye
Abeona Therapeutics 2018 R&D Day AIM TM Capsids Demonstrate Enhanced Delivery to the Eye AAV8 - CMV AAV5 - CMV AAV8 Subretinal Intravitreal 10 Days post - injection in mice AAV110 AAV204 AAV214 Ref: Khabou et al.2016 Intravitreal Case Study AAV2 - 7m8 AAV5 - 7m8 AAV8 - 7m8 91
Slide 92: Intravitreal Administration of AAV204 to NHP Eye
Abeona Therapeutics 2018 R&D Day Intravitreal Administration of AAV204 to Non - Human Primate (NHP) Eye • TIME: 6 WEEKS POST INJECTION Explant culture In vivo PIS POS RPE ONL INL GC Widespread Retinal Transduction 92
Slide 93: AAV204-GFP NHP Intravitreal Administration
Abeona Therapeutics 2018 R&D Day AAV204 - GFP NHP Intravitreal Administration Demonstrates Significant Distribution and Expression – Live Eye Imaging Abeona NHP study comparisons: • Administered 1.5E12 vg • Assessed at 6 weeks • Assessed 50% earlier and at 30% of dose compared to others 93
Slide 94: AAV204 Transduction in Peripheral Retina and Foveal Region
Abeona Therapeutics 2018 R&D Day Green: GFP Red: Rhodopsin Blue: Dapi Intravitreal Administration of AAV204 Results in Significant Transduction in the Peripheral Retina and Foveal Region 94
Slide 95: AAV204 Transduces Rods and Cones in Macula
Abeona Therapeutics 2018 R&D Day AAV204 Efficiently Transduces Rods & Cones in Macula in Non - human primate Retina After Intravitreal Injection Rod Cell Cone Cell Green: GFP Red: Rhodopsin Blue: Dapi Non - human primate eye injected with AAV204.GFP 95
Slide 96: Summary: AIM vectors enable clinical translation for eye diseases
Abeona Therapeutics 2018 R&D Day Summary: AIM TM vectors enable clinical translation for eye diseases • 80% of genetic eye disorders occur in the photoreceptors • Intravitreal delivery of small volume gene therapies can occur in out - patient clinics • Mouse studies identified multiple AIM TM vector
Slide 97: AIM for Cystic Fibrosis (CF)
Abeona Therapeutics 2018 R&D Day Gavin Living with CF AIM TM for Cystic Fibrosis (CF) Source: cff.org
Slide 98: ABO-401 (AIM AAV204.CFTR) for CF
Abeona Therapeutics 2018 R&D Day ABO - 401 (AIM TM AAV204.CFTR) for CF • CF is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time • CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR) • CF af
Slide 99: Historical Challenges to CF gene therapy
Abeona Therapeutics 2018 R&D Day Historical Challenges to CF gene therapy : 1. Packaging CFTR in an AAV is size restricted 2. Delivery of AAV to lung cells Opportunity : new AIM vector with lung tropism - novel transgene + AIM capsid L lung R lung Liver Kidney Ex vivo organ imaging AAV204 demonstrat
Slide 100: ABO-401 corrects CFTR chloride current in CF mice
Abeona Therapeutics 2018 R&D Day ABO - 401 is a membrane - localized CFTR transgene that Corrects CFTR chloride current in CF mice ABO - 401 induces Cl - specific current (FLIPR) Control AAV204 - CFTR ABO - 401 dose dependent induction of Cl - specific current Control AAV204.CFTR 5E5 AAV204 - CFTR 2
Slide 101: ABO-401 Can Address All CFTR Mutations
Abeona Therapeutics 2018 R&D Day ABO - 401 Can Address All CFTR Mutations Human delta508 CF bronchial cells polarized airway cultures with AAV204 - GFP Human delta508 CF nasal epithelial cells polarized airway cultures with AAV204 - GFP Apical Delivery Basolateral Delivery ABO - 401 produces CFTR th
Slide 102: ABO-401 Corrects delta-F508 mutation
Abeona Therapeutics 2018 R&D Day V e h i c l e A A V 2 0 4 V e h i c l e A A V 2 0 4 V e h i c l e A A V 2 0 4 V e h i c l e A A V 2 0 4 0 2 4 6 8 Stimulated CFTR (CF3) currents Δ I s c ( µ A / c m 2 ) HNE (168) HNE (221) HBE (CFL) HBE (06F) W T F 5 0 8 d e l - l u c F 5 0 8 d e l - C F 3 ( 1 1 d a
Slide 103: ABO-401 – Advancing Gene Therapy for All CF Mutations
Abeona Therapeutics 2018 R&D Day • AAV - 204 efficiently targets lung cells • ABO - 401 corrects the underlying CF chloride channel deficit • ABO - 401 can address all CFTR mutations, including delta - F508 (50 - 60% of human population) • Transduces human CF patient bronchial and nasal epithelial c
Slide 104: Panel: Engineering AAV for Improved Infectivity, Tropism Onset of Expression
Abeona Therapeutics 2018 R&D Day Tim Miller, Ph.D. Steven Gray, Ph.D. Mitch Drumm, Ph.D. Panel: Engineering AAV for Improved Infectivity, Tropism Onset of Expression
Slide 105: Abeona Therapeutics 2018 R&D Day
Abeona Therapeutics 2018 R&D Day