Newcelx Ltd. · NASDAQ:NCEL
Newcelx — NLS Pharmaceutics — Investor Presentation (September 2023)
49 slides from Newcelx's investor presentation, Sep 13, 2023
Slide 1: Redefining Central Nervous System Therapies
1 Re defining Central Nervous System Therapies NLS Pharmaceutics September 2023
Slide 2: Forward-Looking Statements
2 Forward - Looking Statements This presentation contains express or implied forward - looking statements within the Private Securities Litigation Reform Act of 1995 and other US Federal securities laws. For example, we are using forward - looking statements when we discuss the results of our clinic
Slide 3: General Overview
General Overview
Slide 4: Business Highlights
4 Business Highlights NLS develops drug treatments for rare and complex Central Nervous System (CNS) disorders • Mazindol ER has successfully completed the Phase 2 trials, including OLE, for narcolepsy treatment: projected to be $4.5B annual market by 2027* • AMAZE Phase 3 Program to start in 2H 202
Slide 5: NLS Leadership Team
NLS Leadership Team Alex Zwyer, MBA Chief Executive Officer & Co - Founder A co - founder of the company with extensive operational, C - level pharmaceutical experience. A serial entrepreneur and strong leader with a proven track - record to get “deals done”. Served as Chief Operating Officer at Vif
Slide 6: Experienced Team Assembled
6 Marianne Lambertson, MSc, MSW Head of Corporate Communications and Investor Relations Harvey Kushner Sr. Biostatistical Consultant Tom Curatolo, MBA Head of US Commercial Operations Beat Widler, PhD Head of Quality Hervé Girsault, MBA Head of Business Development & Licensing Christina Allgeier US
Slide 7: NLS Pipeline Overview
NLS Pipeline Overview Phase 3 Phase 2 IND enabling Preclinical Compound Indication Therapeutic Area Over 100 patents in over 140 countries including technology, mechanism of action and application for: • Sleep Disorders including Narcolepsy, Idiopathic Hypersomnia, and Kleine - Levin Syndrome • ADHD
Slide 8: Narcolepsy Type 1+2, Idiopathic Hypersomnia, Kleine-Levin Syndrome
Narcolepsy Type 1+2 (NT1+2) Idiopathic Hypersomnia (IH ) Cataplexy Refreshing naps Disrupted sleep Sleep paralysis Sleep - related hallucinations No cataplexy Excessive daytime sleepiness (e . g . , ESS > 10 ) MSLT sleep latency <8 min Sleep inertia May have long sleep (> 11 h/day) May remit spontan
Slide 9: Narcolepsy at a Glance
Narcolepsy at a Glance
Slide 10: Narcolepsy: Debilitating Disorder; Large and Underserved Market
10 1. www.ncbi.nlm.nih.gov/pmc/articles/PMC6492289/ 2. Polaris Market Research (April 2023) 3. 2018 National Know Narcolepsy Survey. https://knownarcolepsy.com/hcp/impact Narcolepsy Debilitating Disorder; Large and Underserved Market • 3 Million people suffer worldwide • 200,000 in the US alone • 60
Slide 11: Severe Rare Disease with Unmet Medical Need
11 12% Thought their narcolepsy symptoms are completely or mostly under control 93% Expressed frustration with current treatment options 94% Stated that new treatment options are needed Severe Rare Disease with Unmet Medical Need 78% - 85% of patients in Phase 3 trials for Xyrem® required stimulant
Slide 12: Currently FDA-Approved Treatments
Currently FDA - Approved Treatments Safety Considerations Common AE’s Dose MOA Medicine May reduce effectiveness of oral contraceptives; May increase HR and BP Anxiety , back pain, diarrhea, dizziness, dyspepsia, headache, insomnia , and nausea 100 - 400mg/ 50 - 250mg Dopamine reuptake inhibitor Mod
Slide 13: Challenges of Sodium Oxybate (SXB)
Challenges of Sodium Oxybate (SXB) COMPLIANCE & DOSING • High pill burden: 9000mg/d • Food effect: no intake <2 hrs prior to SXB • Night - time dosing at 10:30PM • Immediate lay down after intake Sources Carter et al. (2014) Patients' Journeys to a Narcolepsy Diagnosis: A Physician Survey and Retros
Slide 14: Market Dynamics in Narcolepsy 2022-2026
Market Dynamics in Narcolepsy 2022 – 2026* Growth originating from North America *Technavio Report (2022) Market is fragmented with only a handful of players. • Market leader: Jazz • Big Pharma not present 2021 2026 Growing Market CAGR with accelerating momentum 9.1% $1.6B 44%
Slide 15: Mazindol ER (3mg)
Mazindol ER (3mg)
Slide 16: Mazindol ER dual SNDRI/OX2R agonist
• Long history of the active ingredient (mazindol) used to treat narcolepsy (“Compassionate Use” Programs) • Novel dual mechanism of action with partial Orexin - 2 receptor activation & triple monoamine reuptake inhibition • Positive Phase 2 results: met most endpoints with high statistical signific
Slide 17: Mazindol: History & Mechanism of Action
17 Mazindol: History & Mechanism of Action Wakefulness Release of Dopamine Nucleus accumbens Tuberomammilary nucleus (histamine) Ventral tegmental area (dopamine) Raphe nuclei serotonin Locus coeruleus norepinephrine • Mazindol has been commercialized in the US and in Europe during the 1970’s - 2000
Slide 18: Mazindol ER Clinical Development Program POLARIS
Mazindol ER Clinical Development Program POLARIS
Slide 19: POLARIS: Mazindol ER Development Program in Narcolepsy
19 POLARIS: Mazindol ER Development Program in Narcolepsy The Mazindol ER development program POLARIS consisted of two US clinical trials • NLS - 1021 Phase 2, A four - week double - blind, placebo controlled, randomized, US multi - center study of Mazindol ER 3 mg once daily vs. placebo (1:1) • NLS
Slide 20: NLS-1021 Study Design and Objectives
20 Primary objective: • Evaluate the efficacy of Mazindol ER in the treatment of excessive daytime sleepiness in adult subjects with narcolepsy type 1 (NT1) or narcolepsy type 2 (NT2) Additional objectives: • Evaluate the safety and tolerability of Mazindol ER in adult subjects with NT1 or NT2. • Ev
Slide 21: Phase 2 Primary Efficacy Results: Excessive Daytime Sleepiness
Phase 2 Primary Efficacy Results Excessive Daytime Sleepiness (EDS)
Slide 22: Primary Analysis: ESS Total Score
22 Primary Analysis: ESS Total Score – Total Study Population (NT1 + NT2) Least Squared Means (LS Means) Mazindol ER (N = 33) Placebo (N = 34) Visit 17.9 (2.97) 18.0 (3.05) ESS Score Baseline 12.7 (5.92) 15.9 (3.85) ESS score Week 1 Day 7 2mg - 4.3 (1.13) - 1.1 (1.06) LS Means CFB Difference from Ba
Slide 23: Change from Baseline in ESS Total Score by Visit
23 Placebo (n = 34) Mazindol ER (n = 33) Total Study Population (NT1 + NT2) Observed Mean (+/ - Standard Error) Change from Baseline in ESS Total Score by Visit 0 2 4 6 8 10 Baseline Week 1 (Day 7 ) Week 2 (Day 14 ) Week 3 (Day 21 ) Week 4 (Day 28 ) Mean (+/ - Standard Error) Change from Baseline in
Slide 24: Phase 2 Secondary Efficacy Results: Cataplexy
Phase 2 Secondary Efficacy Results Cataplexy
Slide 25: Secondary Analysis: Average Weekly Cataplexy Episodes
25 Secondary Analysis: Average Weekly Cataplexy Episodes (NT1 population) Observed Means Change from Baseline (Mean CFB) Mazindol ER (N = 11) Placebo (N = 12) Visit 16.05 (10.2) 15.58 (10.3) Weekly Episodes Baseline 6.85 (5.3) 13.85 (14.6) Weekly Episodes Week 1 Day 7 2mg - 9.65 (10.1) - 1.72 (6.8)
Slide 26: Average Weekly Cataplexy Episodes by Visit
Average Weekly Cataplexy Episodes by Visit Mean Changes from Baseline (NT1 Population) Change from Baseline in Average Weekly Number of Cataplexy Episodes (Mean +/ - SE) Placebo (n = 12) Mazindol ER (n = 11) p = 0.0499 p = 0.1909 p = 0.0372 p = 0.019
Slide 27: ESS & Cataplexy Scores for Approved Treatments vs. Mazindol ER
27 ESS & Cataplexy Scores for Approved Narcolepsy Treatments vs. Mazindol ER Narcolepsy trial & No. of patients Treatment duration Cataplexy decrease vs baseline Baseline Weekly cataplexy episodes ESS decrease from baseline Baseline ESS scores Dose Drug, Sponsor Pivotal trial n=172 12 weeks - - - -
Slide 28: Summary Efficacy Results
28 Summary Efficacy Results • Clinically meaningful improvement on both Sleepiness and Cataplexy at 4 weeks treatment vs placebo • Fast onset of action (within 1 week) even on 2 mg • Sustained EDS and cataplexy improvements at all time points despite small sample size • Strong placebo effect did not
Slide 29: Phase 2 Results: Safety & Tolerability
Phase 2 Results Safety & Tolerability
Slide 30: Tolerability Profile
30 Tolerability Profile Mazindol ER (n=33) Placebo (n=34) Treatment Emergent Adverse Events (TEAEs) 16 (48.5%) 8 (23.5%) Any TEAE 11 (33.3%) 3 (8.8%) Any Treatment - Related TEAE 0 0 Any Severe TEAE 0 0 Any Serious TEAE 0 0 Any TEAE Leading to Drug Discontinuation Mazindol ER (n = 33) Placebo (n = 3
Slide 31: Summary Safety Results
31 Summary Safety Results • No patients discontinued due to adverse reactions • All adverse events where either mild or moderate • None of the adverse events were severe • Most resolved spontaneously (no intervention was required) • No unexpected adverse events • Mazindol ER was well - tolerated, wi
Slide 32: Open Label Extension Study Results: Efficacy
Open Label Extension Study Results Efficacy
Slide 33: Reduction of Excessive Daytime Sleepiness (EDS)
33 6.0 8.0 10.0 12.0 14.0 16.0 18.0 20.0 DB Baseline (Day 1) DB Final (Day 28) OLE Month 1 OLE Month 2 OLE Month 3 OLE Month 4 OLE Month 5 OLE Month 6 Normal Range Placebo Mazindol ER Double - Blind study Open Label Extension study NLS - 1022 Reduction of Excessive Daytime Sleepiness (EDS) Combined
Slide 34: Reduction of Weekly Cataplexy Episodes
34 Double - Blind study Open Label Extension study NLS - 1022 Reduction of Weekly Cataplexy Episodes Combined DB and OLE studies: 4 & 24 weeks 6.0 Placebo 4.0 Mazindol ER 2.0 0.0 8.0 10.0 12.0 14.0 16.0 18.0 DB Baseline (Day 1) DB Final (Day 28) OLE Week 4 OLE Week 8 OLE Week 12 OLE Week 16 OLE Week
Slide 35: Case Study: Subject 1070-001
35 18 16 14 12 10 8 6 4 2 0 DB study 20 DB BL DB W 1 DB W 2 DB W 3 DB W 4 W 1 W 2 W 3 W 4 W 5 W 6 W 7 W 8 W 9 W 10 W 11 W 12 W 13 W 14 W 15 W 16 W 17 W 18 W 19 W 20 W 21 W 22 W 23 W 24 Total ESS Subject 1070 - 001 Open Label Extension study Case Study: Subject 1070 - 001 Combined DB and OLE studies
Slide 36: Open Label Extension Study Results: Safety & Tolerability
Open Label Extension Study Results Safety & Tolerability
Slide 37: OLE Tolerability
37 Tolerability Total (n = 52) MZD MZD (n = 24) PBO MZD (n = 28) TEAE 7 (13.5%) 3 (12.5%) 4 (14.3%) Dry Mouth 5 (9.6%) 2 (8.3%) 3 (10.7%) Covid - 19 4 (7.7%) 0 4 (14.3%) Constipation 4 (7.7%) 3 (12.5%) 1 (3.6%) Urinary Tract Infection 3 (5.8%) 1 (4.2%) 2 (7.1%) Nausea Total (n = 52) MZD MZD (n
Slide 38: POLARIS: OLE Conclusions
38 POLARIS: OLE Conclusions • This 6 - month OLE narcolepsy study showed good subject participation (87%) and retention (71%), especially given the exclusion of any narcolepsy/depression/anxiolytic medications • High treatment compliance with few drug down - titrations reported (11.5%) • Solid effic
Slide 39: Phase 3 Program NLS-1031, NLS-1032 and NLS-1033
39 Phase 3 Program NLS - 1031, NLS - 1032 and NLS - 1033
Slide 40: Phase 3 Narcolepsy Program
40 Phase 3 Narcolepsy Program Two identical placebo - controlled Phase 3 trials investigating Mazindol ER vs placebo, plus a 12 - month extension study NLS - 1033 • Open - label, one - year extension for participants completing NLS - 1031 and NLS - 1032 NLS - 1031 NLS - 1032 Summer 2023 Fall 2023 20
Slide 41: Parallel Design Studies
41 Parallel Design Studies • Population: ~50 NT1 participants treated with Mazindol ER or PBO for 8 weeks (1:1) • Dose: 3 mg once daily, no titration • Primary endpoint: Weekly Cataplexy Episodes from baseline to week 8 • An electronic diary will be completed daily for the week preceding the study v
Slide 42: 12-Month OLE Study (NLS-1033)
42 12 - Month OLE Study (NLS - 1033) • Study Design: A 52 - week, open - label, multi - center study of Mazindol ER 3 mg once daily • Study population: ~100 participants (Completers from studies NLS - 1031 and NLS - 1032) • Rescue narcolepsy/psychiatric medications allowed in the study • Primary obj
Slide 43: Mazindol ER (3mg) Competitive Advantages
Mazindol ER (3mg) Competitive Advantages
Slide 44: Mazindol ER May Represent a Convenient Once-Daily Monotherapy Option
44 If approved, Mazindol ER May Represent a Convenient Once - Daily Monotherapy Option for Narcolepsy Simple, ONCE - DAILY, MONOTHERAPY , 30 - minutes before breakfast Effective on BOTH Cataplexy and Excessive Sleepiness as well as other symptoms of Narcolepsy RAPID onset of action Favorable drug -
Slide 45: Mazindol ER vs. Approved Narcolepsy Treatments
Provigil/Nuvigil Adderall Sunosi Wakix Xyrem/Xyvav/Lumryz Mazindol ER Common AEs Anxiety, back pain, diarrhea, dizziness, dyspepsia, headache, insomnia, and nausea Decreased appetite, insomnia, upset stomach, anxiety, mood changes, dizziness, headache, elevated BP Anxiety, decreased appetite, headac
Slide 46: Timeline
Timeline
Slide 47: Anticipated Development Timeline
47 *Timelines are subject to change. There is no guarantee as to the success of any clinical trial. In addition, there is inherent risk and variability in the overall regulatory process. Approval by the FDA may not be granted, or the FDA may require different study parameters from those that are int
Slide 48: Mazindol ER Competitive Advantages
48 Novel MOA partially targeting the orexin system Validated safety & efficacy of drug substance in chronic use Clinically meaningful improvements on Sleepiness and Cataplexy Schedule IV: low potential for abuse, misuse & diversion Very low drug - drug interaction potential Rapid onset of therapeuti
Slide 49: Redefining Central Nervous System Therapies
49 Redefining Central Nervous System Therapies
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