Slide 1: OV935 (TAK-935) Phase 1b/2a Trial Results
CONFIDENTIAL 1 OV935 (TAK-935) Phase 1b/2a Trial Results December 17, 2018 Exhibit 99.2
Slide 2: Agenda and Speakers
Agenda Speakers Agenda Item Lora Pike Investor Relations & Public Relations Welcome Jeremy Levin, DPhil, MB, BChir Chairman & CEO OV935 and DEE Amit Rakhit, MD, MBA Chief Medical & Portfolio Management Officer Phase 1b/2a Results Jacqueline French, MD Professor of Neurology at NYU Langone Medical Ce
Slide 3: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate" and similar expressions (as well as other words or expressions referencing future e
Slide 4: OV935 and DEE
OV935 and DEE Jeremy Levin, DPhil, MB, BChir Chairman & Chief Executive Officer
Slide 5: Developmental and Epileptic Encephalopathies – A Significant Unmet Need
DEE encompass a heterogeneous group of >10 rare epilepsies with ~100-200,000 patients in the US, including: Duplication 15q (Dup15q) syndrome – prevalence ~1:30,0001 CDKL5 deficiency disorder (CDD) – prevalence ~1:45,000 - 1:60,000 and increasing with genetic testing2,3,4,5 Dravet syndrome (DS) – pr
Slide 6: OV935: Mechanism of Action
CH24H is a brain-specific enzyme for cholesterol catabolism 24HC is a clinically monitorable plasma marker that appears to correlate with active target engagement OV935: Mechanism of Action OV935 T In Plasma In Brain *CH24H, cholesterol 24‑hydroxylase ; 24HC, 24S-hydroxycholesterol CH24H Pathway is
Slide 7: OV935: First in Class Inhibitor
1Barker-Haliski et al.,Cold Spring Harb Perspect Med. 2015 2Mast N, et al. J Biol Chem. 2017 3Sodero AO, et al. EMBO J. 2012 4Paul SM, et al. J Neurosci. 2013 5Sun MY, et al. J Neurophysiol. 2016 6Linsenbardt AJ, et al. Neuropharmacology. May address underlying mechanisms behind refractory seizures
Slide 8: Phase 1b/2a Trial Highlights and Key Learnings
Phase 1b/2a Trial Highlights and Key Learnings Highlights Continue to open sites and enroll eligible patients in ENDYMION Continue dose and titration schedule in Phase 2 ELEKTRA & ARCADE trials Amend ongoing ELEKTRA & ARCADE protocols to: Prohibit concurrent administration of perampanel Extend treat
Slide 9: Phase 1b/2a Trial Design & Baseline Characteristics
Phase 1b/2a Trial Design & Baseline Characteristics Amit Rakhit, MD, MBA Chief Medical & Portfolio Management Officer
Slide 10: OV935 Phase 1b/2a Clinical Trial Design
Key endpoints Primary endpoint Safety and tolerability Secondary and exploratory endpoints Pharmacokinetics (PK) parameters 24S-Hydroxycholesterol (24HC) plasma levels Change in seizure frequency from baseline Trial design Two-part trial* Part 1: Randomized, double-blind, placebo-controlled, titrati
Slide 11: Patient Disposition and Demographics
Part 2 (60 days) Baseline/screening Completed (n=14) Part 1 Withdrawal† † (n=2) Screened (n=26) Screen failure* (n=8) Placebo (n=4) OV935 (n=14) Withdrawal† (n=2) OV935 (n=16) (30 days) Safety and PK assessments Safety, PK, and exploratory efficacy assessments (28-42 Days) Did not meet entrance crit
Slide 12: Heterogeneous Patient Population – Multiple Concomitant AEDs
* Diazepam excluded; generally taken as needed and not as a scheduled medication † All patients prescribed concomitant AEDs Diagnoses Total (N=18) Lennox-Gastaut Syndrome 6 Epileptic Encephalopathy†† 6 Partial Seizures with Secondarily Generalization 1 Frontal Lobe Epilepsy 1 Tuberous Sclerosis Comp
Slide 13: Results: Primary Endpoints – Safety and Tolerability
RESULTS Primary Endpoints – Safety and Tolerability
Slide 14: OV935 Was Generally Well Tolerated With Favorable Safety Profile
*There were no deaths across OV935 and placebo treatment arms †Four patients discontinued due to AEs in OV935 treatment arms; Part 1: weakness (n=1); difficulty with walking/worsening lethargy (n=1); Part 2: seizure cluster (n=2) † † All SAEs were seizure clusters in three patients. † † Safety set:
Slide 15: Observed Effects of OV935 in Patients on Perampanel
An increase in seizures was observed in all three patients who were taking OV935 concomitantly with perampanel All three patients completed the trial, but two down-titrated to 100mg BID in the open label phase (Step 2) Perampanel will be a prohibited concomitant therapy in the ongoing ELEKTRA and AR
Slide 16: Results: Secondary and Exploratory Endpoints
RESULTS Secondary and Exploratory Endpoints – PK, 24HC, and Seizure Frequency
Slide 17: OV935 Reduced Plasma 24HC vs Placebo
Plasma 24HC concentration assessed at baseline, pre-dose at Days 11-85, and Day 121 (~30 days following the end of the Treatment) Plasma 24HC (ng/mL) On OV935 in both Part 1 and Part 2 On Placebo and who cross-over to OV935 after Day 31 4 13 4 12 4 7 4 OV935 plasma levels confirm PK/PD modeling and
Slide 18: OV935 Reduced Seizure Frequency Over Time in Part 2
69 85 92 n=16 n=14 n=14 69 85 92 n=13 n=11 n=11 *The total seizures are based on a period of 28 days on and prior to a specific study day; the first dose day is Study Day 1 Exploratory Analysis: OV935 Reduced Seizure Frequency Over Time in Part 2 Open-label Period
Slide 19: OV935 Treatment Reduced Seizure Frequency
Exploratory Analysis: OV935 Treatment Reduced Seizure Frequency Median Seizure Frequency OV935* Includes patients on perampanel OV935** Excludes patients on perampanel Reduction from Baseline in Seizure Frequency Day 92 (measured from Day 65-92) 45% (n=14) 61% (n=11) Day 85 (measured from Day 58-85)
Slide 20: Change in Seizure Frequency vs. Plasma 24HC
Percent change in seizure frequency vs plasma 24HC in Part 2 treatment period Correlation Coefficient (p-value) Day Pearson Spearman Day 85 (n=6) 0.7747 (0.0704) 0.6957 (0.1248) Day 92 (n=6) 0.7962 (0.0581) 0.9856 (0.0003) Time 24 HC Seizure Day 11 Day 11 Day 2 - 11 Day 31 Day 31 Day 22 - 31 Day 85
Slide 21: Summary: OV935 Phase 1b/2a Trial in Adults with DEE
Primary endpoints: Safety and Tolerability SUMMARY OV935 Phase 1b/2a Trial in Adults with DEE OV935 had a favorable safety profile and was generally well tolerated; most AEs were mild PK OV935 plasma levels were dose proportional Seizure frequency 61% reduction in median seizure frequency was observ
Slide 22: OV935 Clinical Development Program for DEE
Dup15q syndrome CDKL5 syndrome Lennox-Gastaut syndrome Dravet syndrome ARCADE: Phase 2 Open-label pilot trial ~30 pediatric patients ELEKTRA: Phase 2 Double-blind, placebo-controlled trial 126 pediatric patients Primary endpoint: Safety and tolerability Phase 1b/2a Adult patients Primary endpoint: P
Slide 23: Next Steps for Clinical Development
OV935 Broad Clinical Development Program ELEKTRA and ARCADE Trials in Pediatric Patient Populations Continue to initiate sites and enroll eligible patients in the ENDYMION open-label extension trial Continue dose and titration schedule being used in the Phase 2 ELEKTRA & ARCADE trials Amend ELEKTRA/
Slide 24: Clinical Perspectives
Clinical Perspectives Jacqueline A. French, MD Professor of Neurology, NYU Comprehensive Epilepsy Center
Slide 25: Novel Mechanisms of Action are Needed to Treat Refractory Seizures
Refractory seizures do not respond to medicines that exert anti-seizure effect through same target or MOA as marketed AEDs Approximately 100,000- 200,000 US Population with Rare Seizure Disorders* Illustrative purposes only 1 out of 3 PATIENTS Small number achieve seizure freedom with addition of 1
Slide 26: Robust Preclinical Data on Potential Anti-Epileptogenesis Mechanism of OV935
Robust Preclinical Data Across Several Well-Established Models on Potential Anti-Epileptogenesis Mechanism of OV935 OV935 Preclinical and non-clinical findings suggest potential of: Survival benefit in two transgenic epilepsy models Anti-inflammatory and glial modulatory activity contributing to dis
Slide 27: Question & Answer Session
Question & Answer Session Jeremy Levin, DPhil, MB BChir Chairman & CEO Amit Rakhit, MD, MBA Chief Medical & Portfolio Management Officer Jacqueline A. French, MD Professor of Neurology, NYU Comprehensive Epilepsy Center
Slide 28: Thank you to patients, families, caregivers and clinicians
Ovid Therapeutics would like to thank the patients, families, caregivers, and clinicians for their support and active involvement in the OV935 Phase 1b/2a trial