Exhibit 99.1
Corporate Presentation JANUARY 2020
Disclaimer Certain information contained in this presentation and statements made orally during this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and Prevail Therapeutics, Inc.’s (“Prevail”) own internal estimates and research. While Prevail believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. While Prevail believes its internal research is reliable, such research has not been verified by any independent source. This presentation contains forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results and other future conditions. All statements other than statements of historical facts contained in this presentation, including statements regarding future results of operations and financial position, business strategy, current and prospective product candidates, planned clinical trials and preclinical activities, product approvals, degree of market acceptance of approved products, research and development costs, current and prospective collaborations, timing and likelihood of success, plans and objectives of management for future operations, and future results of anticipated product candidates, are forward- looking statements. The words ”may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The forward-looking statements in this presentation represent our views as of the date of this presentation. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. New risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. There can be no assurance that the opportunity will meet your investment objectives, that you will receive a return of all or part of such investment. Investment results may vary significantly over any given time period. The appropriateness of a particular investment or strategy will depend on an investor’s individual circumstances and objectives. We recommend that investors independently evaluate specific investments and strategies. C O N F I D E N T I A L 2
Prevail Therapeutics overview • PR001 Phase 1/2 PROPEL trial for Parkinson’s with GBA mutation (PD-GBA) Large Market & Near-Term currently recruiting; PD-GBA affects >90K Americans Value Inflection for PR001 • Potential for rapid proof-of-concept for PR001 in neuronopathic Gaucher disease; IND active and planned to enter the clinic in first half of 2020 • Potential disease-modifying targets identified based on human genetics Precision Genetic Medicine • Targeting genetically defined patient populations Approach Increases POS • Gene delivery with AAV9 vector has a track record of efficacy and safety High Value Pipeline • PR006 planned to enter clinic in 2020; PR004 IND planned for 2021 Programs • Additional genetically-validated targets in Parkinson’s, Alzheimer’s, ALS, FTD Excellence in CNS Gene • Expertise in developing therapies for neurodegenerative diseases Therapy • Leaders in gene therapy manufacturing and process development C O N F I D E N T I A L 3
Rapid execution in developing gene therapies for patients with urgent unmet needs 2017 2018 2019 AUGUST 2017: MARCH 2018: MARCH 2019: JUNE 2019: Seed financing and $75M Series A $50M Series B $125M IPO REGENXBIO license OCTOBER 2017: MAY 2018: MAY 2019: OCTOBER 2019: Lab space secured REGENXBIO second PR001 PD-GBA 50+ employees in NYC agreement IND active DECEMBER 2019: PR001 nGD IND active C O N F I D E N T I A L 4
Management and Board of Directors Experienced Management Team Board of Directors Francois Nader, MD Asa Abeliovich, Non-Executive Chairman Brett Kaplan, MD MD, PhD Chief Financial Officer CEO and Founder Asa Abeliovich, MD, PhD CEO and Founder Tim Adams Independent Yong Dai, PhD Carl Gordon, PhD, CFA Chief Technology Emily Minkow OrbiMed Officer Chief Business Officer Ran Nussbaum Pontifax Morgan Sheng, MBBS, Ph.D., FRS Franz Hefti, PhD Independent Jeff Sevigny, MD Chief Development Chief Medical Officer Officer Peter Thompson, MD OrbiMed C O N F I D E N T I A L 5
Pipeline of disease-modifying AAV9 gene therapies for neurodegenerative diseases Stage of Development Upcoming Programs Indication Approach Milestones Discovery Preclinical Phase 1/2 Pivotal GBA1 • Interim Phase 1/2 data PD-GBA IND Active Gene Transfer in 2H of 2020 PR001 Neuronopathic GBA1 • Phase 1/2 initiation Gaucher disease Gene Transfer IND Active • Interim Phase 1/2 data FTD-GRN GRN • Phase 1/2 initiation PR006 Gene Transfer • Interim Phase 1/2 data GBA1 Gene Synucleinopathies Transfer + • IND enabling studies PR004 á-Synuclein • IND filing Knockdown Prevail owns worldwide commercial rights to all product candidates in the pipeline C O N F I D E N T I A L 6
Precision genetic medicine approach to neurodegenerative diseases Mutated Gene Disease I N F L A M M A T I O N S U B S T R A T E A C C U M U L A T I O N D Y S F U N C T I O N A L L Y S O S O M E P A T H W A Y P R O T E I N C E L L T O X I C I T Y A G G R E G A T I O N • Human genetic studies have identified genes that cause or increase risk of neurodegenerative diseases • Many of these genes are involved in lysosomal function • Gene therapy can enable delivery of a functional gene to the CNS • We plan to develop our therapies for genetically-defined patient populations with corresponding mutations
C O N F I D E N T I A L 7 AAV9 is well-suited to deliver functional genes or gene knockdown to the CNS Viral transduction and Gene cargo AAV9 delivery vector CNS administration transgene expression • AAV9-based therapy has shown transformative efficacy and safety and is now approved for SMA • The effectiveness of AAV9-based therapies is due to its ability to distribute broadly across the CNS • AAV9 manufacturing process is well-characterized and scalable • Prevail has licensed exclusive WW rights to AAV9 from REGENXBIO to deliver the genes in our lead programs C O N F I D E N T I A L 8
PR001 overview • AAV9 viral vector delivering the GBA1 gene, which encodes PR001 glucocerebrosidase (GCase) Route of • Single intra-cisterna magna (ICM) injection Administration • Parkinson’s disease with at least one GBA1 mutation (PD-GBA) o Earlier disease onset, more rapid progression, and higher rate of Lead Indications dementia than sporadic PD • Neuronopathic Gaucher disease (nGD) o Neurological form of Gaucher due to severe GCase deficiency • PD-GBA IND active and sites initiated for Phase 1/2 PROPEL trial Progress and Status • nGD IND active and site activation in process for Phase 1/2 PROVIDE trial for Type 2 Gaucher disease C O N F I D E N T I A L 9
Parkinson’s disease Prodromal Period After Clinical Diagnosis Of PD • Early disease manifests with non-motor and subtle motor symptoms • With disease progression motor symptoms worsen Psychosis Complications and cognitive & behavioral symptoms emerge disability Fluctuations of Dyskinesia • Benefit of existing Dysphagia Motor symptomatic therapies Postural instability Degree Freezing of gait diminishes as disease Falls Bradykinesia progresses Rigidity Tremor Non • No disease-modifying Urinary symptoms - Pain EDS Fatigue Orthostatic hypotension therapy available Hyposmia Dementia motor Constipation RBD MCI Depression -20 -10 0 10 20 Time (years) Source: Kalia and Lang, Lancet 2015; 386: 896 RBD: REM behavioral sleep disorder; EDS: excessive daytime sleepiness; MCI: mild cognitive impairment C O N F I D E N T I A L 10
PD-GBA and neuronopathic GD are a continuum of pathology with the same underlying genetic mechanism Number and severity of GBA1 mutations âžœ Decreasing enzyme activity âžœ Increasing disease severity 1 1 2 2 0 mild / moderate severe mild / moderate severe mutations mutation mutation mutations mutations “Sporadic” PD-GBA with less PD-GBA with more Type 1 Gaucher Neuronopathic Parkinson’s severe phenotype severe phenotype disease Gaucher disease C O N F I D E N T I A L 11
PR001 mechanism of action in PD-GBA Parkinson’s PR001 Disease Treated WITH GBA1 MUTATION C O N F I D E N T I A L 12
PR001 CBE mouse model efficacy results Activity and substrate reduction Activity and substrate reduction Efficacy (CBE dose-ranging efficacy study) (CBE 6-month efficacy study) (CBE dose-ranging efficacy study) GCase Activity GCase Activity Astrogliosis (glial scarring) GluSph GluSph Rotarod Means are presented +/- SEM. *: p<0.05; **: p<0.01; ***: p<0.001. By one-way ANOVA and Fischer’s exact test for glial scarring. For rotarod, nominal p values were calculated by linear regression in the CBE-treated groups, with gender corrected for as a covariate. Activity, substrate and astrogliosis (glial scarring) measured in the cortex C O N F I D E N T I A L 13 PR001 low dose = 1.3x1010 vg/g brain, PR001 mid dose = 4.2x1010 vg/g brain, PR001 high dose = 1.3x1011 vg/g brain
PR001 genetic mouse model efficacy results Activity Substrate reduction Efficacy GCase Activity GluSph Beam Walk • PR001 increased GCase enzyme • 4L/PS-NA mice exhibited glycolipid • 4L/PS-NA mice exhibited motor activity (cortex) accumulation behavior dysfunction • PR001 suppressed lipid accumulation • PR001 improved motor function in a (cerebellum) beam walk test Control + Vehicle 4L/PS-NA + Vehicle 4L/PS-NA + 7.4x109 vg/g brain PR001 4L/PS-NA + 7.4x1010 vg/g brain PR001 4L/PS-NA + 2.3x1011 vg/g brain PR001 4L/PS-NA + 7.4x1011 vg/g brain PR001 Each bar represents the mean ± SEM P-value: *p<0.05, ***p<0.001 by one-way analysis of variance followed by Tukey HSD C O N F I D E N T I A L 14 †: p<0.1 for effect of PR001 injected dose by multiple linear regression for genotype and dose across all animals
PR001 safety and biodistribution in NHPs NHP biodistribution with ICM delivery Frontal Cortex 0.00e+00 9.93e+01 2.55e+05 Vector Genomes Hippocampus 0.00e+00 4.68e+03 5.81e+04 • NHP high dose equivalent to per ug DNA tissue starting clinical dose for Periventricular Tissue 0.00e+00 5.00e+02 2.17e+03 PD-GBA (allometric scaling) 1.00e+06 Putamen 0.00e+00 6.94e+01 1.37e+04 1.00e+05 Ventral Midbrain 0.00e+00 1.28e+03 1.51e+04 1.00e+04 • No PR001-related safety events or adverse findings Cervical Spinal Cord 0.00e+00 1.07e+05 1.62e+05 1.00e+03 were observed 0.00e+00 Thoracic Spinal Cord 0.00e+00 1.54e+05 3.23e+05 Lumbar Spinal Cord 0.00e+00 8.91e+04 2.69e+05 Control Low Dose High Dose Control Dose = 0 vg/g brain, Low Dose = 6.2 x 1010 vg/g brain PR001, High Dose = 2.3 x 1011 vg/g brain PR001 N=3 per group C O N F I D E N T I A L 15
PR001 PD-GBA PROPEL Phase 1/2 trial Randomized, double-blind, sham procedure-controlled Single ICM 3 month 12 month 5-year safety and injection biomarker readout clinical readout clinical follow-up PD-GBA Patients PR001 Low Dose vs. Placebo (N=8, 6:2) • Single or biallelic GBA1 mutations • Moderate to severe Parkinson’s disease • Stable background PD medication PR001 High Dose vs. Placebo (N=8, 6:2) • Safety and tolerability • Key biomarkers: GCase, GluCer, GluSph (CSF and blood) • Additional biomarkers: á-Synuclein, NfL, DAT SPECT, MRI • Efficacy: MDS-UPDRS, cognition, ADLs ICM: intra-cisterna magna; MDS-UPDRS: Movement Disorders Society Unified Parkinson’s disease Rating Scale; ADLs: Activities of Daily Living; NfL: neurofilament light; DAT: Dopamine transporter; SPECT: single photon emission computed tomography C O N F I D E N T I A L 16
Goal of PR001 treatment is to deliver the GBA1 gene to restore GCase activity in PD-GBA patients GCase Enzyme Activity (Illustrative) Pre-PR001 Treatment Goal of PR001 Treatment ~70-80% - GBA ~50% PR001 PD Upside of PR001 100% Treatment • Human genetics suggest increasing GCase activity by 20-30% of healthy levels expected to be clinically meaningful • Similarly, mouse data suggests 20-30% increase in GCase activity corresponds to efficacy C O N F I D E N T I A L 17
PR001 Type 2 Gaucher disease PROVIDE Phase 1/2 trial Open label Single ICM 3-6 month 12 month 5-year safety and injection biomarker readout clinical readout clinical follow-up Type 2 Gaucher Patients • Infants 0-24 months old • Biallelic GBA1 mutations • Neurological signs & symptoms PR001 (Open label, N=15) consistent with Type 2 Gaucher disease • Stable SoC background medications • Safety and tolerability • Key biomarkers: GCase, GluCer, GluSph (CSF and blood) • Time to clinical event (e.g., tracheostomy, PEG placement, death) • Efficacy: behavior, cognition, gross motor, function, QoL ICM: intra-cisterna magna; QoL: quality of life; SoC: standard of care; PEG: percutaneous endoscopic gastrostomy C O N F I D E N T I A L 18
PR001 Type 3 Gaucher disease PROGRESS Phase 1/2 trial Planned, open label Single ICM 3-6 month 12 month 5-year safety and injection biomarker readout clinical readout clinical follow-up Type 3 Gaucher Patients • Children 1-12 years old • Biallelic GBA1 mutations • Neurological signs & symptoms PR001 (Open label, N=21) consistent with Type 3 Gaucher disease • Stable use of ERT • Safety and tolerability • Key biomarkers: GCase, GluCer, GluSph (CSF and blood) • Efficacy: behavior, cognition, gross motor, function, QoL ICM: intra-cisterna magna; QoL: quality of life; ICM: intra-cisterna magna; QoL: quality of life; ERT: enzyme replacement therapy C O N F I D E N T I A L 19
PR001 market opportunity PD-GBA Neuronopathic GD • Type 2 Gaucher: Severe progressive neurologic • PD patients with at least one GBA1 mutation Disease disease; mortality by age 2 • Earlier onset, faster progression, and higher Overview • Type 3 Gaucher: Juvenile or adult onset with prevalence of dementia multiple neurological manifestations • No effective therapies for the neurologic • No therapies to slow or stop disease progression Treatment & manifestations of Gaucher • Benefit of symptomatic therapies diminishes as Unmet Need • ERTs used for peripheral manifestations; do not disease progresses enter the brain • Parkinson’s prevalence 7M worldwide, 1M in US • >1,000 patients in the major markets Market Size • 7-10% of PD patients worldwide have GBA1 • 6% of Gaucher cases in the US but higher mutation prevalence in other regions Source: Lancet Neurol 2018; 17: 939–53, N Engl J Med. 2009 Oct 22; 361(17): 1651–1661, Lancet Neurol. 2012 Nov; 11(11): 986–998, Parkinson’s Prevalence Project, Hematology. 2017 Mar;22(2):65-73; J Hum Genet. 2017 Aug;62(8):763-768; J Pediatr. 2015 Jan;166(1):172-7; Arch Intern Med. 2000 Oct 9;160(18):2835-43; J C O N F I D E N T I A L Pediatr. 2017 Nov;190:130-135 Independent Market Research (N=25) March 2019 20
PR006 overview PR006 • AAV9 viral vector delivering the GRN gene, which encodes progranulin Route of • Single intra-cisterna magna (ICM) injection Administration • Frontotemporal dementia with GRN mutation (FTD-GRN) Lead Indications o Rapidly progressive dementia impacting behavior and language o Leads to death within 3-10 years • Mouse efficacy and NHP safety and biodistribution studies conducted Progress and Status • On track to initiate Phase 1/2 clinical trial in 2020 C O N F I D E N T I A L 21
Frontotemporal dementia with GRN mutation is caused by progranulin deficiency Healthy Brain FTD-GRN N E U R O N S U R V I V A L N E U R O N A L C E L L D E A T H N O R M A L R E D U C E D • FTD pathology includes P R O G R A N U L I N P R O G R A N U L I N neurodegeneration and L Y S O S O M A L inflammation L Y S O S O M E D Y S F U N C T I O N • Progranulin is a secreted factor that is enriched in lysosomes • Progranulin deficiency leads to lysosomal N E U R O N N E U R O N dysfunction A G G R E G A T E S P R O G R A N U L I N D E G R A D E D P R O D U C T S Source: Zhou et al, Nature Communications (2017) C O N F I D E N T I A L 22
Number of GRN mutations causes varying degrees of progranulin deficiency resulting in spectrum of disease Number of GRN mutations žœ Decreasing progranulin âžœ Increasing disease severity 0 1 2 mutation mutations mutations (Heterozygous) (Homozygous) Healthy Frontotemporal Neuronal Ceroid Individuals Dementia Lipofuscinosis (Adult onset) (Childhood onset) C O N F I D E N T I A L 23
PR006 efficacy in human FTD-GRN neuronal cultures iPSC-derived neurons from Secreted progranulin Progranulin Secreted expression progranulin Cathepsin Secreted D maturation progranulin Insoluble TDP-43 levels FTD-GRN mutation carriers 0.6 n Control 0.6 n 0.6 i o i o Control Control a t a t entration entr FTD-GRN #1 (M1L) entr FTD-GRN #1 (M1L) FTD-GRN #1 (M1L) 0.4 FTD- 0.4 #2 (R493X FTD-GRN 0.4 #2 (R493X) FTD-GRN #2 (R493X) c Secreted Progranulin n c L) PGRN (ng/mL) simple n c L) con 5 co m / co / m n 0.6 g g o n n (ng/mL) lin ( Control lin ( #1 ati 4 0.2 n u 0.2 n u 0.2 ntr a FTD-GRN a #1 (M1L) e ein) c t 3 (ng/mL) mL)rogr0.4 FTD-GRN rogr #2 (R493X) n ro Progranulin 0.0g/P 0.0 P 0.0 o p n 5 5 5 c 0 8x10 ( 0 8x10 0 8x10 n 2 PR006A (MOI) PR006A (MOI) PR006A (MOI) (ng/mg PGRN 0.2 granuli 1 Progranulin Pr o 0 0.0 Control l FTD- FTD- Excipient PR006 o 1 2 t r GRN # #1 GRN # #2 n N N PR006 (MOI) o R R C G G—-D D T T • iPSC-derived F neurons F from • PR006 transduction resulted • PR006 treatment rescued the • PR006 treatment decreased humans with FTD-GRN in robust expression of defective maturation of insoluble TDP-43, a hallmark mutations secreted less progranulin protein secreted cathepsin D, a key lysosomal of FTD-GRN pathology progranulin than neurons into the cell media protease derived from healthy controls Statistics determined using a t-test; * = p < 0.05, ** = p < 0.01, ** = p < 0.001. Data is presented as mean ± SEM. C O N F I D E N T I A L 24
PR006 efficacy in Grn knockout mice Progranulin expression Substrate reduction Neuroinflammation Progranulin mRNA Lipofuscin accumulation Neuroinflammation (cerebral cortex) (hippocampus) (Tnf mRNA) (cerebral cortex) • PR006 dose-dependently increased • PR006 dose-dependently • PR006 treatment reduced gene expression of the GRN transgene reduced accumulation of lipofuscin, an expression of proinflammatory cytokine indicator of lysosomal dysfunction, TNF⺠(Tnf) throughout the brain Means are presented +/- SEM. N=8-10 per group. ***: p<0.001 by ANOVA followed by Dunnett’s multiple tests correction comparing each group to excipient-treated Grn KO mice. C O N F I D E N T I A L 25
PR006 safety and biodistribution in NHPs Progranulin Expression in CSF Results * • PR006 administration resulted in widespread transduction in the CNS t and periphery, and elevated 2—Excipien progranulin protein levels in the CSF from • No adverse PR006-related findings 1—Change (clinical and histopathological Fold endpoints) 0—Excipient Low High • Third-party pathologist classified Dose Dose “extremely minor” degree of nerve fiber degeneration in spinal cord and • PR006 treatment dose-glial cellularity in DRGs dependently increased progranulin expression in the CSF NHPs received ICM administration of excipient, low dose PR006, or high dose PR006 Bars represent mean ± SEM. P-value: *p<0.05, by one-way dose dependence response analysis using William’s trend test C O N F I D E N T I A L 26
PR006 FTD-GRN PROCLAIM Phase 1/2 trial Planned Single ICM 3 month 12 month 5-year safety and injection biomarker readout clinical readout clinical follow-up FTD-GRN Patients • 30-80 years old • Single pathogenic GRN mutation PR006 • Symptomatic disease stage • Stable background medications • Safety and tolerability • Key biomarkers: progranulin, NfL • Additional biomarkers: volumetric MRI, markers of neuroinflammation and astroglial pathology • Efficacy: CDR plus NACC FTLD; measures of behavior, cognition, language, function, QoL ICM: intra-cisterna magna; NfL: neurofilament light chain; CDR plus NACC FTLD: Clinical Dementia Rating plus National Alzheimer’s Coordinating Center Frontal Temporal Lobar Dementia; QoL: quality of life C O N F I D E N T I A L 27
PR006 market opportunity FTD-GRN Disease • Progressive and devastating early-onset form of dementia Overview • Leads to death within 3-10 years Treatment & • No therapies approved for FTD Unmet Need • No therapies have shown disease modification • FTD prevalence ~50,000 in US; ~800-110,000 in EU Market Size • 5-10% of FTD patients have a GRN mutation Source: Rascovsky et al. 2005; Riedl et al, 2014, Neuropsychiatric Disease and Treatment, 10:297-301; European Medicines Agency bvFTD website, Gass et al, 2006, Human Molecular Genetics C O N F I D E N T I A L 28
CMC strategy and capabilities Established internal process development capabilities; working with CDMOs to supply clinical trials with drug product Phase 3 and Commercial Material Phase 1/2 Material • Baculovirus platform to establish high-yield scalable process • Robust adherent HEK293 process to • Process development and scale up underway; has maximize speed to the clinic demonstrated promising yield and potency • Partnership with established CDMO • Partnered with Lonza to develop and manufacture drug supply for late-stage clinical trials and commercial production using baculovirus platform • Comparability studies and assessments underway C O N F I D E N T I A L 29
Prevail Therapeutics summary • Developing potentially disease-modifying gene therapies for neurodegenerative disorders • PR001 Phase 1/2 trial for PD-GBA currently recruiting • PR001 Phase 1/2 trial for nGD on track to initiate in first half of 2020 • Pipeline of gene therapy programs for neurodegenerative diseases using a precision genetic medicine approach • Multiple catalysts for PR001 and PR006 expected in 2020, including several active clinical trials and data readouts