Inhibikase Therapeutics, Inc. · NASDAQ:IKT
Inhibikase Therapeutics — Investor Day (March 2023)
38 slides from Inhibikase Therapeutics's investor day presentation, Mar 22, 2023
Slide 1: Inhibikase Neurodegeneration R&D Day
Exhibit 99.1 March 22, 2023| Inhibikase Neurodegeneration R&D Day Transforming fundamental and clinical research in neurodegenerative disease Inhibikase.com : IKT
Slide 2: Disclaimer
DISCLAIMER This presentation shall not constitute an offer to sell or a solicitation of an offer to buy any securities, nor shall there be any sale of such securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification unde
Slide 3: Agenda for the 2023 Neurodegeneration R&D Day
Agenda for the 2023 Neurodegeneration R&D Day • Why is c-Abl an important target in PD? • How was IkT-148009 discovered? • What is therapeutically possible with IkT-148009? • Clinical Development: Phase 2 and beyond in PD • Opening of MSA clinical development In Inh hiib biik ka as se e.c .co om m •
Slide 4: Company Highlights: Multi-Therapeutic Pipeline
COMPANY HIGHLIGHTS: MULTI-THERAPEUTIC PIPELINE Multi-Indication Pipeline in Neurodegeneration, Oncology and Infectious Disease (1). ‘Clinical Development’ progress 1 3 bars represent the current state of the CLINICAL DEVELOPMENT BIOMARKER indicated programs. Blue arrows represent completed or in pro
Slide 5: Parkinson's Disease in the U.S.
1 Parkinson’s Disease in the U.S. By 2025, Parkinson’s disease Chronic Disease for a Long Time 930,000 – 1,200,000 drug sales are expected to 1 1/3 of a Patient’s Lifespan = 25 years U.S. Patients DOUBLE Pharma Insights, 2019 60,000 38,000 60 New Cases / Year Deaths / Year Average Age Of Onset Sales
Slide 6: Discovery of c-Abl's Role in PD
Discovery of c-Abl’s Role in PD In Inh hiib biik ka as se e.c .co om m • • :: IK IKT T 6 6
Slide 7: What is c-Abl and how do we monitor activation?
What is c-Abl and how do we monitor activation? 1 c-Abl is an essential regulator of growth and differentiation 245 Ø Monitoring c-Abl activation by observation of Tyr phosphorylation (Y245p) 1 Neural Regen Res. 2022 Feb; 18(2): 237–243 Inhibikase.com • : IKT 7
Slide 8: Demonstrating c-Abl activation is required for neurodegeneration in PD
DEMONSTRATING c-ABL ACTIVATION IS REQUIRED FOR NEURODEGENERATION IN PD 1,2 Slowly progressive, a-synuclein dependent models were essential to thinking differently about PD Inherited dysfunctional α-synuclein: After 12 Months A53T mutation Quantitative readout Sporadic dysfunctional of neuronal funct
Slide 9: Aggregates in absence of c-Abl do not lead to neurodegeneration
DEMONSTRATING c-ABL ACTIVATION IS REQUIRED FOR NEURODEGENERATION IN PD α-synuclein aggregates in the ABSENCE OF c-Abl DO NOT LEAD TO NEURODEGENERATION No c-Abl gene = No neurodegeneration Injection (Inj) of an expression vector for the A53T form of synuclein doesn’t degrade neurons until the express
Slide 10: Development of a functional screening model
DEVELOPMENT OF A FUNCTIONAL SCREENING MODEL Use acute neurotoxin MPTP as a functional screen for 1 drug selection Dopamine neurons are selective Commercial inhibitors show varied activities IC 50 148009 (09): 33 nM 148032 (32): 53 nM 1427 (427) : 30 nM 1 Karuppagounder et al., Sci. Transl Med 1/18/2
Slide 11: Potential for c-Abl inhibition to protect neurons in the brain
DEMONSTRATING THE POTENTIAL FOR c-Abl INHIBITION TO PROTECT NEURONS IN THE BRAIN 1 Pre-treatment with IkT-148009 blocks neurodegeneration in the MPTP acute toxicity model No IkT-148009 Pre-Treatment with IkT-148009 Mice treated with an acute neurotoxin MPTP Mice pre-treated with IkT-148009 are prote
Slide 12: Initial conclusions
Initial conclusions What we concluded early on about c-Abl inhibition as a potential 1 disease-modifying therapy for PD? Ø C-Abl is an essential determinant for PD initiation and progression: If you delete the gene, you cannot induce neurodegeneration in animals Ø C-Abl inhibition can block inductio
Slide 13: Discovery of IkT-148009 and its potential therapeutic benefit in PD
Discovery of IkT-148009 and its potential therapeutic benefit in PD In Inh hiib biik ka as se e.c .co om m • • :: IK IKT T 13 13
Slide 14: Properties essential to build into a c-Abl inhibitor
What properties were essential to build into a c-Abl inhibitor? 1 RAMP as a discovery engine for PD Re-engineering goals: Ø Over come PGP efflux from brain back to blood Ø Suppress GI and hematological AEs Ø High potency and wide therapeutic dosing range 1 Karuppagounder et al., Sci Transl. Med, Jan
Slide 15: IkT-148009 is a selective inhibitor of non-receptor tyrosine kinases
IS A SELECTIVE INHIBITOR OF NON-RECEPTOR TYROSINE KINASES IkT-148009 is Low Toxicity, Selective, Brain Penetrant c-Abl Inhibitor in Clinical Development 1 TOXICOLOGY IN RAT/MONKEY Human equivalent dose of 1460 mg Imatinib Dasatinib Nilotinib IkT-148009 Cardiovascular None 120 Renal None Liver None 1
Slide 16: Functional response in a model of inherited disease
FUNCTIONAL RESPONSE IN A MODEL OF INHERITED DISEASE Therapeutic dosing in a slowly progressive model of inherited 1 disease leads to functional recovery Baseline Neuromuscular Toxic Levels of Synuclein Near Normal Behavior Returned Coordination Are Introduced Into One Following Treatment Behavioral
Slide 17: Functional response in a model of inherited disease
FUNCTIONAL RESPONSE IN A MODEL OF INHERITED DISEASE Therapeutic dosing in a slowly progressive model of inherited 1 disease leads to functional recovery 148009 148009 Vehicle Vehicle Controls Controls 148009 1 Karuppagounder et al., Sci Transl Med Jan 18 2023 Inhibikase.com • : IKT 17
Slide 18: Functional response in a model of inherited disease
FUNCTIONAL RESPONSE IN A MODEL OF INHERITED DISEASE Therapeutic dosing in a slowly progressive model of inherited 1 PD suppresses c-Abl activation 148009 Vehicle Controls 1 Karuppagounder et al., Sci Transl Med Jan 18 2023 Inhibikase.com • : IKT 18
Slide 19: Functional response in a model of inherited disease
FUNCTIONAL RESPONSE IN A MODEL OF INHERITED DISEASE Therapeutic dosing in a slowly progressive model of inherited 1 PD is neuroprotective 148009 Vehicle Controls Control Lesioned Hemisphere Hemisphere 148009 1 Karuppagounder et al., Sci Transl Med Jan 18 2023 Inhibikase.com • : IKT 19
Slide 20: Functional response in a model of idiopathic disease
FUNCTIONAL RESPONSE IN A MODEL OF IDIOPATHIC DISEASE a Therapeutic dosing leads to reduction/clearance of -synuclein 1 aggregates at 6 months 1 Karuppagounder et al., Sci Transl Med Jan 18 2023 Inhibikase.com • : IKT 20
Slide 21: Therapeutic benefit of once daily oral IkT-148009 in animal models
THERAPEUTIC BENEFIT OF ONCE DAILY ORAL IkT-148009 IN ANIMAL MODELS Modeling PD followed by therapeutic dosing revealed: Ø C-Abl inhibition is neuroprotective in animal models of disease Ø C-Abl inhibition blocks downstream effector pathways of neurodegeneration in animal models of disease Ø C-Abl in
Slide 22: Understanding biochemical therapeutics
UNDERSTANDING BIOCHEMICAL THERAPEUTICS Model of the biochemistry of disease initiation and its treatment response Disease Treatment Normal, intracellular processes clear a-synuclein aggregates 1 Werner and Olanow37, 6-15 (2022) Inhibikase.com • : IKT 22
Slide 23: Clinical Development of IkT-148009 for Treatment of Parkinson's disease
Clinical Development of IkT-148009 for Treatment of Parkinson’s disease Inhibikase.com • : IKT 23
Slide 24: Phase 1/1b/2a Trial Summary
PHASE 1/1b/2a TRIAL SUMMARY Demographics and Adverse Events Across 113 Healthy Subjects and Patients Healthy Subjects Value Parkinson Patient Value Category Demographic (% of Total N=88) (% of Total, N=25) Gender Female 34 (38.6) 9 (36) Male 54 (61.4) 15 (60) Age Average (SD) 57.9 (5.72) 61.9 Median
Slide 25: Phase 1/1b/2a Trial in Safety and Dosing
PHASE 1/1b/2a TRIAL IN SAFETY AND DOSING Complete Listing of Possibly Category Dose mg Dose # Occurrences # Occurrences Severity Duration Healthy PD patients Subjects (N=25) Drug-related Adverse Events: (N=88) Cardiovascular 75 mg Single Dose 1 Mild 1 Palpitations No Clinically Significant Adverse G
Slide 26: Ongoing Trials in Safety and Dosing: Phase 2 '201' Trial
ONGOING TRIALS IN SAFETY AND DOSING CLINICAL PHASE 2: the ‘201’ Trial 3 doses Double-blinded Enrollment and Measurement 3 months Analysis Open-label 12 month safety extension at 3 doses March23 u 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Double-blinded: 3 Months Dosing Across 3 Doses 12 month ext
Slide 27: Ongoing Trials in Safety and Dosing: Phase 2 '201' Trial
ONGOING TRIALS IN SAFETY AND DOSING CLINICAL PHASE 2: the ‘201’ Trial 3 doses Double-blinded Enrollment and Measurement 3 months Analysis Open-label 12 month safety extension at 3 doses March23 u 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Double-blinded: 3 Months Dosing Across 3 Doses 12 month ext
Slide 28: Ongoing Trials: Adding back 200 mg dose and vision monitoring
ONGOING TRIALS IN SAFETY AND DOSING CLINICAL PHASE 2: the ‘201’ Trial 3 doses Double-blinded Enrollment and Measurement 3 months Analysis Open-label 12 month safety extension at 3 doses March23 u 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Adding back 200 mg dose post-Clinical Hold: Vision Monitori
Slide 29: Clinical Development of IkT-148009 for Treatment of Multiple System Atrophy (MSA)
Clinical Development of IkT-148009 for Treatment of Multiple System Atrophy (MSA) In Inh hiib biik ka as se e.c .co om m • • :: IK IKT T 29 29
Slide 30: Discriminating MSA from PD
DISCRIMINATING MSA FROM PD What distinguishes MSA from PD? PD MSA Ø Slowly progressive, 25 years to death Ø Rapid progression, 8 years to death Ø Highly variable interpatient variation in rate of progression Ø Similarity in disease manifestation and rate of and disease manifestation progression Ø Mu
Slide 31: Synuclein aggregates are phosphorylated by c-Abl in MSA patient brain
SYNUCLEIN AGGREGATES ARE PHOSPHORYLATED BY C-ABL IN MSA PATIENT BRAIN 1 C-Abl activation occurs in glial cells in MSA and in models NHP model 1 Marmion, Werner, Kordower et al, (2021) Neurobiol Dis 148:105184 Inhibikase.com • : IKT 31
Slide 32: Analyzing therapeutic and prophylactic benefit in MSA
ANALYZING THERAPEUTIC AND PROPHYLACTIC BENEFIT IN MSA IkT-148009 inhibition protects against loss of function Inhibikase.com • : IKT 32
Slide 33: c-Abl may have a wider role in other diseases
C-Abl MAY HAVE A WIDER ROLE IN OTHER DISEASES C-Abl Activation 1 MSA AD ALS Prog Neurobiol. 2021;202:102031 J Neurol Sci. 2018;393:80-82 Autophagy. 2021;17(5):1278-1280. Sci Transl Med. 2017;9(391):eaaf3962 J Biol Chem. 2020 ;295(23):7905-7922 Front Cell Neurosci. 2015 9;9:203 Front Cell Neurosci. 2
Slide 34: Planned Phase Program: Phase 2 '202' Trial
PLANNED PHASE 2 PROGRAM CLINICAL PHASE 2: the ‘202’ Trial 2 doses Double-blinded Enrollment and Measurement 6 months Analysis Month? u 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Double-blinded: 6 Months Dosing Across 2 Doses Primary: Safety/Tolerability Exploratory: a-synuclein aggregate level in
Slide 35: 2023 Catalysts
2023 CATALYSTS 2023 Guidance in Neurodegeneration PD MSA Ø Fully enroll the 201 trial Ø Complete prophylactic and therapeutic animal Ø Initiate long-term extension study model studies Ø Prepare for Phase 3 program Ø Initiate MSA Phase 2 in US and EU with positive Ø Declare a commercial formulation:
Slide 36: Selected Stock and Financial Data
Selected Stock and Financial Data In Inh hiib biik ka as se e.c .co om m • • :: IK IKT T 36 36
Slide 37: Company Highlights: Selected Financial and Stock Data
COMPANY HIGHLIGHTS Selected Financial and Stock Data Capitalization Table January 30, 2023 September 30, 2022 Balance Sheet (last reporting period) Common Shares Outstanding 28,027,840 Current Assets: Options (WAEP: $2.41) 4,001,208 Cash, Cash Equivalents, $26,534,208 Warrants (WAEP: $0.77) 22,423,9
Slide 38: Contact
CONTACT E: info@inhibikase.com PH: 678-392-3419 GEORGIA OFFICE 3350 Riverwood Parkway Suite 1900 Atlanta, GA 30339 MASSACHUSETTS OFFICE 1 Cranberry Hill Suite 200 Lexington, MA 02421 Inhibikase.com : IKT