a breakthrough in parkinson's. - biocre · • 2016-2026 cagr = 11.1% • new us approvals...

A breakthrough in Parkinson's. Copyright © 2018 NOS Life Sciences Corp. - All rights reserved. This document contains proprietary and confidential information of NOS Life Sciences Corp. The contents of this document may not be disclosed to third parties or duplicated in any form, in whole or in part, without prior written permission.

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Imagine increasingly losing the ability to move, sleep, or smile.

While being completely aware of what is happening.

This is what Parkinson’s Disease can feel like.


Parkinson’s Disease is a neurodegenerative condition that progressively takes away the ability to move.

Problem (1/2)

Time

Autonomy / Motor Functionality

Y2 Y5 Y12Onset

• Nearly Normal

• Partial autonomy • Reduced work

capacity

• Severely Impaired • Caretaker needed • Cannot work

• Total dependance

Parkinson’s Disease Progression

Average years in disease progression.


Gold-standard treatment (Levodopa) helps to partially recover movement but presents critical unmet needs.

• Only partial recovery of movement.

• Causes Dyskinesia -permanent uncontrollable movements- which leads: - to a diminished autonomy / ability to function - to eventually stop treatment, leaving patients prostrated.

• Does not stop disease progression

Levodopa Limitations

Problem (2/2)


Lipea®: a breakthrough add-on therapy that would significantly increase patient quality of life.

• Enhancement of movement recovery by 100%*;

• Reduction of dyskinesia by 48%*; allowing for: - a better quality of life - added years of life with autonomy (i.e. extended

Levodopa therapeutic lifespan)

• Deceleration of disease progression by 79%*.

Solution (1/3)

Sources: (1) Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014),

17, 455–468. (2) Ramiro González-Aparicio et al. OEA reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson ́s disease. Neurobiology of Disease 62 (2014), 416–425.

Patient Benefit Goals

* As observed in pre-clinical trials.


Solution (2/3)

A highly effective therapeutic with no side-effects registered to date.

Key cellular signaling molecules and pathways: a) TPRV1 membrane receptors b) PPAR-alpha receptor c) MAPK - signaling pathways d) GPR119 membrane receptors

Mechanism of Action

Neuroprotective Action

Anti-dyskinetic Action

Description Lipea® is a pharmaceutically optimized formulation of OEA, an endogenous neuromodulator.


Less side effects will allow Levodopa to be dosed for more years,

also improving patients’ lives.

Reduced dyskinesia, will allow doctors to increase

Levodopa dose and improve patient’s quality

of life.

These patients end up prostrate with no available

options.

Dyskinesia causes many patients to ultimately abandon Levodopa

treatment.

Solution (3/3)

Patients will benefit from optimized, extended use of Levodopa with Lipea®.



Dyskinesia Reduction (2): • Axial dyskinesia: -48% • Forelimb dyskinesia: -50% • Orolingual dyskinesia: -48% • Contralateral rotations: -50%


100% improvement in motor functionality and 48% reduction of motor side effects are demonstrated by pre-clinical studies.

Pre-Clinical Results (1/3)

Enhancement of Motor Functionality (1): • Distance: +100% • Speed: +100% • Coordination: 140%




79% deceleration in disease progression is confirmed by Parkinson's pre-clinical study.

(1) Measured by TH+ cell quantity. Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014), 17, 455–468.

(2) Measured by TH+ cell density. Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014), 17, 455–468.


Protects Dopaminergic Neuron Health (2)

99%

Preserves Dopaminergic Neuron Quantity (1)

79%

Parkinson’s Disease constantly attacks and weakens

Dopaminergic Neurons. Eventually, they die.

Body Movement is controlled by Dopaminergic Neurons

• Lipea reaches the brain • Lipea is effective during the entire

duration of dyskinesia symptoms • Lipea is neuroprotective • No toxicity detected • No adverse effects detected • No “wearing-off” detected


Lipea® meets crucial requirements for an effective long-term therapy, as substantiated in pre-clinical studies.

Sources: Ramiro Gonzalez-Aparicio, Fernando Rodriguez de Fonseca et al. The systemic administration of OEA exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology (2014), 17, 455–468. Ramiro González-Aparicio et al. OEA reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson ́s disease. Neurobiology of Disease 62 (2014), 416–425. Suardiaz et al - Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory pain - Pain (2007) Anton et al - OEA prevents neuroimmune HMGB1/TLR4/NF-kB danger signalling in rat frontal cortex and depressive-like behaviour induced by ethanol binge administration - Addiction Biology (2016)


An effective long-term therapy


PD currently affects 13M people worldwide and, due to an aging population, is estimated to affect 32M by 2050.

• 32M by 2050 • Average onset age: 50 • As early as 25

13 M patients worldwide

• US: $26 Bn • Spain: $6.4 Bn • UK: $2.5 Bn

$120 Bn burden

Every hour, 85 people in the world are diagnosed with Parkinson’s disease.

85 new diagnosis per hour

Sources: - Willis AW, et al. (2010). Geographic and ethnic variation in Parkinson disease: a population- based study of US Medicare beneficiaries. Neuroepidemiology; 34: 143–151 - Marras C, Tanner CM. Epidemiology of Parkinson’s disease. In: Watts RL, Koller WC, eds. Movement disorders, neurologic principles and practice, 2nd ed. New York, McGraw Hill, 2004:177–196 - de Lau L and Breteler M. Epidemiology of Parkinson’s disease. Lancet Neurology 2006; 5: 525–35 - Huse DM, Schulman K, Orsini L, et al. Burden of illness in Parkinson's disease. Mov Disord. 2005;20:1449-1454. - Kowal SL, The current and projected economic burden of Parkinson's disease in the United States. Movement Disorder Society Official Journey 2013. - Willis AW, et al. (2010). Geographic and ethnic variation in Parkinson disease: a population- based study of US Medicare beneficiaries. Neuroepidemiology; 34: 143–151. - The social impact of Parkinson’s disease in Spain: Report by the Spanish Foundation for the Brain. Neurologia, 2016. - Gumber A et al, Economic, Social and Financial Cost of Parkinson's on Individuals, Carers and their Families in the UK. Sheffield Hallam University Research, 2016 - The incidence and prevalence of Parkinson’s in the UK. Clinical Practice Research Datalink Summary report 2018.

Market Size (1/2)


Current PD drug market expected to grow at 11.1% CAGR.Market Size (2/2)

PD Drug Sales 7 Major Markets ($ Bn)

0

2

5

7

9

2012 2016 2022 2026

0.8

0.60.60.4

1.8

1.511.2

6.2

2.11.51

US EU5 JPN

• 2016-2026 CAGR = 11.1% • New US approvals expected in coming years • Levodopa represents 38% of the total market

Sources: • Global Data. Parkinson’s Disease Global Drug Forecast and Market Analysis to 2022. June 2015. • Global Data. Parkinson’s Disease Global Drug Forecast and Market Analysis to 2026. May 2018. (1) 7MM: US, Germany, UK, France, Spain, Italy and Japan.

16%

33%51%

US EU5 Jap

14%

25% 60%

2016

2026

Levodopa Sales 7MM ($ Bn)


Compared to alternatives, Lipea® promises to be the best add-on therapy for the foreseeable future.

Sources: https://www.drugs.com/sfx/amantadine-side-effects.html, https://www.addextherapeutics.com/en/news-and-events/press-releases/addex-dipraglurant-positive-phase-2-data-pd-lid-published-leading-peer-reviewed-journal-movement-disorder-society/, https://www.ncbi.nlm.nih.gov/pubmed/25669730, https://www.ncbi.nlm.nih.gov/pubmed/20803300, https://www.ncbi.nlm.nih.gov/pubmed/26990766, https://www.drugs.com/sfx/ketamine-side-effects.html

Amantadine Gocovri

(Approved)

Dipraglurant ADX48621 (Phase II)

Eltoprazine (Phase II)

Levetiracetam (Phase II)

AQW051 (Phase II)

Ketamine (Discovery)

High Medium Medium Low Low Low Low

High Low Low Low Low Low Low

Low High Medium Medium High Medium High

Low None Medium Medium Medium High Medium

All Only Late Stage n/a n/a Only Late

Stage n/a Only Late Stage

Dyskinesia Reduction

Side Effects

Translational Risk

Patients Addressed

1

2

3

4

5

(Pre-Clinical)

Movement Recovery Enhancement

Competitive Landscape (1/2)

https://www.drugs.com/sfx/amantadine-side-effects.html

https://www.addextherapeutics.com/en/news-and-events/press-releases/addex-dipraglurant-positive-phase-2-data-pd-lid-published-leading-peer-reviewed-journal-movement-disorder-society/

https://www.ncbi.nlm.nih.gov/pubmed/25669730



https://www.drugs.com/sfx/ketamine-side-effects.html


Alternative treatments are only recommended in 10% of cases, and are highly invasive and expensive.

Competitive Landscape (2/2)

Sources: Okun M. et al. Guide to Deep Brain Stimulation Therapy. US National Parkinson Foundation, 2017. Soulas T et al. Attempted and completed suicides after subthalamic nucleus stimulation for Parkinson's disease. J Neurol Neurosurg Psychiatry. 2008;79(8):952. Epub 2008 Apr 10 Doshi P et al. Depression leading to attempted suicide after bilateral subthalamic nucleus stimulation for Parkinson's disease. Mov Disord. 2002;17(5):1084.

- Implanted electrodes 12cm into the brain.

- Surgery cost: up to $ 100K.

- May increase the risk for suicide

- Direct infusion via a tube inserted in the intestines.

- Only for advanced cases.

- Costs $ 10K to $ 70K / year, plus surgery

Deep Brain Stimulation (DBS)

Levodopa/Carbidopa Intestinal Gel (LCIG)


An industry-experienced team.Team

Industry Experience:Scientific Background:

CEO Pablo Inones

Operations Ruben Henriquez, PhD

Medical Research Fernando Rodriguez de Fonseca, PhD

Drug Development Tina Garyantes, PhD

Media & Marketing Andy Maier

Bio-Engineering Alcides Nicastro, PhD

Pharmacology Rafael de la Torre Fornell, PhD

Pre-Clinical Research José Lanciego, PhD


What if you had the opportunity to take a good look at the path ahead before starting your trek?


Lipea® allows for a rapid, less expensive, early proof of concept*.

* Pre-IND efficacy assessment as anti-dyskinetic and motor enhancer. ** Investigational New Drug (IND) *** Food for Special Medical Purpose (FSMP) as defined by the European Food Safety Authority (EFSA); and Medical Food (MF) as defined by the US Food and Drug Administration (FDA)

Clinical Development Strategy (1/3)

Rare opportunity to perform early efficacy and safety studies in patients before requesting IND** status.

Active Molecule Features

• Meets criteria for FSMP and MF*** • Endogenous molecule • Therapeutic level within normal physiological range • Excellent safety profile, no adverse effects detected to date • Extensively studied mechanism of action

• Ingredients already in commercial useDelivery System

Preliminary proof of concept will make pharmaceutical clinical development more efficient and less risky.

Why


Current financing round founds our preliminary proof of concept* studies in humans.

Target Validation

Lead Optimization

Chemistry Process

Pre-Clinical Development

Pilot Studies in Humans*

Clinical Phases I & IIDiscoveryDiscovery NDA

Approval

Successfully completed Current Stage

Clinical Phase III

Market

Clinical Development Strategy (2/3)

Objectives: • Preliminary proof of concept* in humans • Translational de-risking of clinical

development • Abbreviate later clinical studies • Gather human data on safety and efficacy

in a cost-effective manner • GLP-GMP preparation for IND

Endpoints: • Patient Quality of Life: Motor Functionality • Pharmacokinetics • Bioavailability • Toxicology / safety

* Pre-IND efficacy assessment as anti-dyskinetic and motor enhancer.


Significantly lower investment to complete Clinical Development*.Clinical Development Strategy (3/3)

Investment to first proof of concept**: € 1M € 37 M

* When compared with typical new chemical entity clinical development. ** Pre-IND efficacy assessment as anti-dyskinetic and motor enhancer.

1st human efficacy data


Recent transactions in the Parkinson’s drug space.

Movement Recovery Enhancement

# Date Asset Developer Buyer Indication/ target Stage Value

1 2018 Jul Eltoprazine® / 5HT1a/b agonist Elto Pharma (US) Amaranthus (US) Levodopa add-on therapy to

reduce dyskinesia Phase II $316M

2 2018 Jul Dipaglurant® / mGLUR5 antagonist

Addex(Switzerland) Stock Appreciation Levodopa add-on therapy to

reduce dyskinesia Phase II €270M

3 2018 Mar Foliglurax® (mGLUR4 agonist)

Prexton Ther. (Netherlands- Switzerland)

Lundbeck A/S (Denmark)

Levodopa add-on therapy to reduce Off period Ph.II € 905 M

4 2017 Aug MEDI1341 anti-alpha synuclein AstraZeneca (UK) Takeda (Japan) Reduce synuclein-induced

neurodegeneration Ph. I €400M

5 2017 Aug Gocovri®: extended release Amantadine Adamas (US) Stock Appreciation Levodopa add-on therapy to

reduce dyskinesia Approved ~$ 450M

6 2016 Aug APL-130277: sublingual Apomorphine Cynapsus (USA) Sunovion (USA) Levodopa add-on therapy to

reduce Off periodPivotal ph.II/III $624M

7 2016 Jan Tozadenant® A2a antagonist Biotie (Finland) Acorda (USA) Levodopa add-on therapy to

reduce Off period Ph.III $363M

Market Dynamics

*

Cases based on new formulations of known drugs.*

*


Out-license or trade-sale deals will provide attractive exit opportunities to investors.

Exit Opportunities

NDA Approval

Lipea® presents the perfect opportunity to boost an aging multi-billion-dollar portfolio of the leading pharmaceutical companies.

Company Value** (€):

Time (years): Today +1.5 +1.5 +2.5

6.5 M 58 M 142 M 600 M

+ 1

1.2 B

Current Stage Next StagesCompleted

Clinical Phase I & II

Discovery & Pre-Clinical Development

Clinical Phase III

Market

Pilot Studies in Humans*

* pre-IND efficacy assessment as Anti-dyskinetic and Motor enhancer. ** Standard valuation method: clinic-probability-discounted net present value over 3-X peak-sales terminal value.

•

OpEx22%

Payroll28%

R&D50%


A € 1M investment expected to yield 6x return in 1½ years.Current Financing Round

Round Values

Capital Requirement € 1 M

Estimated Pre-Money Valuation € 6.5 M

Time Covered 18 months

Estimated Valuation after completion of current stage. € 58 M

Key Use of Proceeds

Standard valuation method: clinic-probability-discounted net present value over 3-X peak-sales terminal value.

[email protected]

www.noslifesciences.com USA: 1241 Canary Island Dr., Weston, FL (33327) Spain: Avenida de Carlos Haya, 75, Málaga, Andalusia (29010)

mailto:[email protected]

http://www.noslifesciences.com

a breakthrough in parkinson's. - biocre · • 2016-2026 cagr = 11.1% • new us approvals...

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