Inhibikase Therapeutics, Inc. · NASDAQ:IKT
Inhibikase Therapeutics — AD-PD 2022
21 slides from Inhibikase Therapeutics's conference presentation, Mar 24, 2022
Slide 1: Parkinson's Disease Modification Through Abl-kinase Inhibition
Exhibit 99.1 IKT Parkinson’s Disease Modification Through Abl-kinase Inhibition AD-PD 2022, March 18 2022
Slide 2: Disclosures
Disclosures Dr. Milton Werner is the Founder, Chief Executive and largest shareholder of Inhibikase Therapeutics, Inc. 2 2
Slide 3: 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 4: Treating Inside and Outside of the Brain
TREATING INSIDE AND OUTSIDE OF THE BRAIN Simultaneous Evaluation of Brain and GI Function Identifies a Potential Disease-Modifying Treatment BY 2025, PARKINSON’S § PD is more than just a disease of the brain, DISEASE DRUG SALES ARE EXPECTED TO § GI manifestation in many patients occurs at an early s
Slide 5: Common Features of Misfolded Protein Diseases
COMMON FEATURES OF MISFOLDED PROTEIN DISEASES 1 Causation in Parkinson’s and Alzheimer’s is closely related What role does the misfolded protein play? 1 Nat. Neurosci. 21: 1332-1340 (2018) 5
Slide 6: The Path to Neurodegeneration
THE PATH TO NEURODEGENERATION Stressors Trigger the Production of Misfolded α-Synuclein 1 Which Activates c-Abl to Drive Neurodegeneration Immunotherapy acts here 1 6 Werner and Olanow, Mov. Disorders 2022 Jan;37(1):6-15.
Slide 7: Activated c-Abl Is the Gateway in the Disease Path
ACTIVATED C-ABL IS THE GATEWAY IN THE DISEASE PATH α-Synuclein ‘Plaques’ Do Not Cause Disease Without c-Abl 1 Modification in Humanized Preclinical Models α-Synuclein plaque in the ABSENCE OF c-Abl CAUSES NO NEURODEGENERATION AFTER 6 MONTHS No c-Abl = No neurodegeneration Injection (Inj) of an expre
Slide 8: The Path to Disease Modification
THE PATH TO DISEASE MODIFICATION Biochemistry of Parkinson’s Disease Initiation and 1 Progression Disease process Treatment effect 1 Werner and Olanow, Mov. Disorders 2022 Jan;37(1):6-15; , J Clin Invest. 2016; 126: 2970-2988, Brain 2019; 142:2380-2401, Cell 2011; 144: 689-702, Nat Neurosci. 2013; 1
Slide 9: IkT-148009 Is a Small Molecule c-Abl Inhibitor
IS A SMALL MOLECULE c-ABL INHIBITOR IkT-148009: Low Toxicity, Selective, Brain Penetrant c-Abl Inhibitor in Clinical Development No organ toxicity Selective Inhibitor of non-Receptor Tyrosine Kinases 1 High brain penetrance c-Abl and Abl2/Arg Imatinib Dasatinib Nilotinib IkT-148009 1 Toxicology in R
Slide 10: c-Abl Inhibition Reverses Functional Loss in Parkinson's Animal Models
MODIFIES DISEASE c-Abl Inhibition by IkT-148009 Reverses Functional Loss in Parkinson’s Disease Animal Models a-Synuclein Toxicity Neurodegeneration Motor Dysfunction Neuroinflammation IkT-148009 clears to IkT-148009 preserves IkT-148009 restores IkT-148009 suppresses baseline in the as much as 85%
Slide 11: Evidence of Functional Recovery in the Gut
EVIDENCE OF FUNCTIONAL RECOVERY IN THE GUT Oral IkT-148009 in Mice Humanized for Parkinson’s Disease in Gut Reverses Functional Loss METHOD OF MEASUREMENT POST TREATMENT RESULTS α-Synuclein Aggregates Introduced At 3 months defecation slows to 500 min (3x normal); At 6 months Into Gut Slows Gut Tran
Slide 12: Effect on Cause of Disease
EFFECT ON CAUSE OF DISEASE Oral IkT-148009 Treatment Nearly Clears Pathological a-Synuclein in the Brain and Gut Clearance of toxicity in the gut Clearance of toxicity in the brain Green: Pathological a-synuclein Red: Neural ganglia in gut Aggregates Nearly cleared during treatment with IkT- 148009
Slide 13: Summary
SUMMARY Key points of Parkinson’s Disease Initiation and 1 Progression § Internalization of misfolded or aggregated a-synuclein and the activation of c-Abl in response is a key event in PD initiation/progression § The long-sought goal of clearing a-synuclein aggregates for a therapeutic purpose shou
Slide 14: Clinical Development and Status
IKT Clinical Development and Status AD-PD 2022, March 18 2022
Slide 15: Phase 1: Safety and Dosing
PHASE 1 TRIAL IN SAFETY AND DOSING Phase 1: Dose Proportional Clinical Pharmacokinetics and No Clinically Significant Adverse Events Category Demographic Value (% of Total N=88) Gender Female 27 (37.5) Male 45 (62.5) Age Average (SD) 57.9 (5.72) Median 58.0 Range 45, 69 Ethnicity Hispanic or Latino
Slide 16: Phase 1: Dose Proportional Clinical Pharmacokinetics
PHASE 1 TRIAL IN SAFETY AND DOSING Phase 1:Dose Proportional Clinical Pharmacokinetics and No Clinically Significant Adverse Events Clinical Pharmacokinetics of IkT-148009-SAD Cmax AUC Linear (Cmax) Linear (AUC) 200000 R² = 0.9977 6000 180000 R² = 0.9905 160000 5000 140000 4000 120000 100000 3000 80
Slide 17: Phase 1b: Mild to Moderate PD Safety
PHASE 1 TRIAL IN SAFETY AND DOSING Phase 1b: Mild to Moderate PD (H&Y < 3.0) and No Clinically Significant Adverse Events Category Demographic Value (% of Total N=8) Gender Female 4 (50) Male 4 (50) Age Average 61 Median 61 Range 57, 65 Ethnicity Hispanic or Latino 1 (12.5) Not Hispanic or Latino 7
Slide 18: Phase 1b: Pharmacokinetics Similar to Elderly Healthy Subjects
PHASE 1 TRIAL IN SAFETY AND DOSING Phase 1b:Pharmacokinetics similar to elderly healthy subjects AUC 0-24 T T C V /F CL 1/2 max max z (ng- (h) (h) (ng/ml) (l) (l/h) h/mL) 15.4 5 1040 12700 32.5 1.52 Day 1 Mean 25 mg 11.3 4 419 6010 14.7 0.905 N=6 SD Healthy 27.4 4.67 1770 25400 42.8 1.1 Day 7 Mean 5
Slide 19: Ongoing Trials: Clinical Phase 1b and Phase 2 Programs
ONGOING TRIALS IN SAFETY AND DOSING Clinical Phase 1b and Phase 2 Programs Multiple Ascending Dose (MAD): 7-Day Dosing Multiple Ascending Dose (MAD): 7-Day Dosing Phase 1b § 3 dosing cohorts, 3:1 randomized with placebo, doses determined from SAD PK and safety ONGOING § 24 patients total § 8 patient
Slide 20: Acknowledgements
ACKNOWLEDGEMENTS Multi-institutional effort across five models Inhibikase Therapeutics, Inc. Parkinson’s Institute Johns Hopkins University Senthil Karuppagounder, PhD Milton H Werner PhD Tyler Molitor, PhD Richard Nguyen MS Roger Rush PhD Cassandra Hempel Shivani Bisen Terence Kelly, PhD Ashani Cha
Slide 21: Q&A
Q&A Targeting c-Abl we believe is transformational to treatment of neurodegeneration 21