Cyclerion Therapeutics, Inc. · NASDAQ:CYCN
Cyclerion Therapeutics — Corporate Update (October 2020)
24 slides from Cyclerion Therapeutics's corporate update, Oct 14, 2020
Slide 1: Delivering impact in CNS diseases - Investor Call
Delivering impact in CNS diseases INVESTOR CALL - OCTOBER 14, 2020
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward - looking statements. Any statements contained in this presentation that are not historical fac ts may be deemed to be forward looking statements. Words such as “anticipate,” “believe,” “potential,” “expect,” “may,” “will,” “should ,” “could,”
Slide 3: Introduction - Peter Hecht, Chief Executive Officer
INTRODUCTION Peter Hecht, Chief Executive Officer 3
Slide 4: Results in healthy elderly subjects
Results in healthy elderly subjects x favorable safety and tolerability x crossed the blood brain barrier (BBB) x pathway target engagement confirmed x delivered rapid, robust, and selective neurophysiological changes 4
Slide 5: Independent expert joining us today
Independent expert joining us today Andrew E. Budson , MD Chief of Cognitive & Behavioral Neurology, Associate Chief of Staff for Education, and Director of the Center for Translational Cognitive Neuroscience, Veterans Affairs (VA) Boston Healthcare System AFFILIATIONS: Associate Director for Resear
Slide 6: Agenda
Agenda Translational pharmacology results 2 Introduction and overview 1 Q&A 4 Strategic focus 3 6
Slide 7: Biomarker-driven early clinical development strategy
Translational pharmacology study in elderly • safety • pharmacokinetics • target engagement • pharmacodynamic biomarkers Phase 1 (completed) • safety • pharmacokinetics • target engagement • pharmacodynamics • dose selection for next study Parallel exploratory Phase 2 studies • focused patient subse
Slide 8: Translational pharmacology study results support advancement
IW - 6463 translational pharmacology study results support advancement In 24 healthy elderly subjects • safe and well tolerated • crosses the blood brain barrier (BBB) at 2 - 3X concentrations needed for pharmacodynamic effect 1 • confirmed target engagement: blood pressure, cGMP in CSF • no effects
Slide 9: Study design and objectives
C6463 - 102 s tudy design and objectives 24 healthy elderly subjects completed period 1 IW - 6463 QD Placebo 15 days 15 days IW - 6463 QD Placebo washout 12 subjects completed both crossover periods* *Period 2 participation was reduced due to Covid - 19 related restrictions in the Netherlands OBJECT
Slide 10: Activity in CNS: neuronal function
Activity in CNS: neuronal function Cellular Bioenergetics Cerebral Blood Flow Neuro Inflammation Neuronal Function Data analysis ongoing No significant effects observed in this healthy elderly study. MELAS study to assess effects of IW - 6463 on dysregulated metabolism in mitochondrial disease Encou
Slide 11: Positive findings on three relevant CNS biomarkers
Positive findings on three relevant CNS biomarkers qEEG : Alpha Power Event - Related Potential (ERP): N200 Saccadic eye movement: reaction time and peak velocity 11
Slide 12: qEEG and basic frequencies
qEEG and basic frequencies EEG - power spectra - analyzing EEG signals in distinct frequency bands • delta - 0 - 4 Hz, associated with deep sleep • theta - 4 - 8 Hz, waking/falling asleep, some association with cognition • alpha - 8 - 14 Hz, passive wakefulness, associated with attention and cogniti
Slide 13: Significantly increases posterior alpha power
IW - 6463 significantly increases posterior alpha power Placebo IW - 6463 IW - 6463 vs. Placebo No effect of placebo on EEG alpha power Significant increase in EEG alpha power with IW - 6463 Significant increase in EEG alpha power with IW - 6463 compared to placebo 13 Day 15: % Change From Baseline
Slide 14: Consistent alpha power effects across repeat sessions
IW - 6463’s consistent alpha power effects across repeat sessions indicate a stable and robust signal DAY 1 PRE - DOSE DAY 15 MEASURES Effect represents up to a 2 - year reversal of alpha power aging after 2 weeks of treatment 14
Slide 15: Increases alpha power with consistent treatment responses
IW - 6463 increases alpha power with consistent treatment responses 60 30 0 - 30 Placebo IW - 6463 Anterior (p = 0.0752) Change from Baseline (%) 15 Statistically significant alpha power increases Change in Closed - Eye Alpha (8 - 12 Hz) Power Persistent, consistent treatment responses Posterior Clo
Slide 16: Event related potential (ERP)
Event related potential (ERP) • latency and amplitude of waveforms impacted in aging and neurodegenerative diseases with cognitive impairment (and other CNS diseases) • participants wear EEG cap and headphones, auditory tones presented with instruction to press a response - button when they hear inf
Slide 17: Improves N200 latency with greater age-associated effect
IW - 6463 improves N200 latency with a greater age - associated effect p=.016 p=.02 • significant latency reduction of N200 response to IW - 6463 in participants treated for 15 days compared to those untreated. • N200 response to IW - 6463 in participants older and younger than 70. • latency respons
Slide 18: Improves N200 latency and effect increases with age
IW - 6463 improves N200 latency and effect increases with age untreated 6463 treated @ day 15 untreated 6463 treated • overall significant decrease in N200 latencies observed on day 15 of IW - 6463 treated participants compared to untreated participants (p<.02) • the effects increased with age and w
Slide 19: Saccadic eye movement, an objective measure of attention
Saccadic eye movement, an objective measure of attention • short, fast, simultaneous tracking of both eyes in the same direction • related brain areas include the frontal cortex, superior colliculus, substantia nigra, and amygdala • may be reflective of attention/arousal and influenced by factors su
Slide 20: Improves eye movement, an objective functional measure
IW - 6463 improves eye movement, an objective functional measure Actual Treatment Mean Mean 0.02 0.00 - 0.02 - 0.04 15 mg IW - 6463 Placebo Mean Mean Change From Baseline in Saccadic Reaction Time (sec) on Day 15 Post - Dose (p=0.0216) Actual Treatment Mean Mean Saccadic Peak Velocity is the average
Slide 21: Advancing in Phase 2 clinical trials
Advancing IW - 6463 in Phase 2 clinical trials 21 Objectives • evaluate safety, tolerability, and pharmacodynamic effects of IW - 6463 in a short - term study • de - risk progression to larger, longer symptomatic and disease modification trials Treatment • once - daily IW - 6463 Enrichment strategy
Slide 22: Our commitment to CNS
Immediate Execution • deepen understanding of biology and powerful pharmacology • MELAS study • ADv study • strategic partnership Portfolio Growth Our commitment to CNS 22 Portfolio Advancement Focused CNS company foundation • capital allocation to CNS development and pipeline building • pursuing a
Slide 23: Thank you for joining
23 Thank you for joining x significant improvements observed in neurophysiological and objective performance measures x moving forward in MELAS and ADv , informed by these data x Phase 2 data in 2021 x CNS focus as a company
Slide 24: Delivering impact in CNS diseases - Investor Call
Delivering impact in CNS diseases INVESTOR CALL - OCTOBER 14, 2020
Cyclerion Therapeutics — Corporate Update (October 2020) on 6ix