Slide 1: Preliminary Results from a Phase 1 Study of ALKS 2680 in Healthy Participants and Patients with Narcolepsy or IH
Brendon Yee,1 Julia Chapman,1 Ron Grunstein,1 Christopher Argent,2 Angela D’Rozario,1 Craig Hopkinson,3 Jandira Ramos,3 Ishani Landry,3 Sergey Yagoda,3 Bhaskar Rege3 1Woolcock Institute of Medical Research, Sydney, Australia; 2Scientia Clinical Research, Ltd., Randwick, Australia; 3Alkermes, Inc., W
Slide 2: Financial Relationship Disclosure
Financial Relationship Disclosure Ineligible companies are those whose primary business is producing, marketing, selling, re-selling, or distributing health care products used by, or on patients. ◻︎ No, I HAVE NOT had a financial relationship with an ineligible company in the past 24 months. ■ Yes,
Slide 3: Forward-Looking Statements
Forward-Looking Statements Certain statements set forth in this presentation constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: the potential therapeutic and commercial
Slide 4: ALKS 2680 Is an Investigational Oral Orexin Receptor Agonist for Narcolepsy
ALKS 2680 Is an Investigational Oral Orexin 2 Receptor Agonist for the Treatment of Narcolepsy ALKS 2680 is a highly potent, orally bioavailable, selective OX2R agonist ≥10 fold more potent than orexin Aa >5,000-fold selectivity relative to OX1Ra Designed to address underlying pathology of narcoleps
Slide 5: Ongoing Randomized, Double-Blind, Placebo-Controlled First-in-Human Study of ALKS 2680
25 mg* 15 mg 8 mg Ongoing Randomized, Double-Blind, Placebo-Controlled First-in-Human Study of ALKS 2680 *Denotes dynamic decision points for triggering subsequent cohorts aIn MAD, participants were dosed for 10 days once daily IH: idiopathic hypersomnia; NT2: narcolepsy type 2; PBO: placebo Healthy
Slide 6: First-in-Human Study of ALKS 2680: SAD and MAD Healthy Volunteers
Ongoing Randomized, Double-Blind, Placebo-Controlled First-in-Human Study of ALKS 2680: SAD and MAD Healthy Volunteers Each dose cohort in both SAD and MAD included 8 new participants 6 on ALKS 2680, 2 on placebo Objectives: Safety and tolerability Pharmacokinetics (PK) and pharmacodynamics (PD) *De
Slide 7: Generally Well Tolerated in Healthy Volunteers in Both SAD and MAD
ALKS 2680 Was Generally Well Tolerated in Healthy Volunteers in Both SAD and MAD Maximum tolerated dose not reached Most AEs were mild and observed at doses ≥15 mg (SAD) and ≥8 mg (MAD) No severe AEs or serious adverse events (SAEs) were reported Most AEs were transient and resolved without interven
Slide 8: Achieved Desired Pharmacokinetic Profile With Once-Daily Dosing
ALKS 2680 Achieved Desired Pharmacokinetic Profile With Once-Daily Dosing Overall PK profile supports once-daily dosing Mimics natural sleep/wake cycle Half life = 8-10 hours Wide safety margin ~100-fold safety multiples for planned therapeutic doses relative to toxicology studiesa 2 metabolites mea
Slide 9: Exhibited CNS Activity in Non-Sleep Deprived Healthy Volunteers
ALKS 2680 Exhibited CNS Activity in Non-Sleep Deprived Healthy Volunteers Correlation Between Beta Power (Objective Measure) and Karolinska Sleepiness Scale (Subjective Measure) Dose-Dependent Increase in Frontal Cortex Beta Power Placebo-corrected percent change from pretreatment baseline Healthy V
Slide 10: First-in-Human Study of ALKS 2680 in Patients With NT1
Ongoing Randomized, Double-Blind, Placebo-Controlled First-in-Human Study of ALKS 2680 in Patients With NT1 NT2 and IH patient cohorts are currently being evaluated at higher doses 1:1:1:1 randomization in a 4-way cross-over design Up to 8 patients per cohort First 4 patients in the NT1 cohort compl
Slide 11: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics Baseline Disease Severity Total (N=4) Narcolepsy Severity Scale, mean (SD) Severe 29-42, very severe 43-54 39.8 (3.50) Epworth Sleepiness Scale, mean (SD) Score >10 suggests excessive daytime sleepiness 16.0 (2.83) Weekly Cataplexy Rate, mean (SD) 9.0 (10.61
Slide 12: Single Doses of ALKS 2680 Were Generally Well Tolerated
Placebo ALKS 2680 Preferred Term n=4 1 mg n=4 3 mg n=4 8 mg n=4 Adverse events (AEs) reported as related to study drug, n (%) 0 0 0 4 (100) Insomnia 0 0 0 3 (75) Pollakiuria 0 0 0 2 (50) Salivary hypersecretion 0 0 0 2 (50) Blood pressure increased 0 0 0 1 (25) Bruxism 0 0 0 1 (25) Dizziness 0 0 0 1
Slide 13: Significantly Improved Sleep Latency With a Clear Dose Response
ALKS 2680 Significantly Improved Sleep Latency With a Clear Dose Response NT1 Patients Change from Baseline in Average Sleep Latency on MWT Over 8 Hours, Least Squares Mean (95% CI), Minutes ALKS 2680 Dose P < 0.001 Average Sleep Latency on the Maintenance of Wakefulness Test (MWT) (N = 4 per dose)
Slide 14: Single Dose Time Course Suggests a Therapeutic Dose Between 3 mg and 8 mg
ALKS 2680 Single Dose Time Course Suggests a Therapeutic Dose Between 3 mg and 8 mg in NT1 NT1 Patients Sleep Latency Mean ± SE, Minutes Maximum test duration = 40 min Day 1 (Post-dose), Hours Maintenance of Wakefulness Test (MWT) 2 4 6 8 Day -1 (Baseline), Hours Dosing 0 NT1: narcolepsy type 1
Slide 15: Conclusions
Conclusions ALKS 2680 in Generally well tolerated up to doses of 50 mg Increased objective and subjective measures of alertness PK/PD profile supports once-daily oral dosing ALKS 2680 in Generally well tolerated at all doses tested; drug-related adverse events only observed at highest dose (8 mg) St
Slide 16: Acknowledgments and Next Steps
Acknowledgments The authors would like to thank: The volunteers and patients who are participating in this study and their families The investigators and research staff This study is sponsored by Alkermes, Inc. Next Steps Additional data to be presented at upcoming conferences Phase 1b study ongoing