Irlab Therapeutics Ab Class A · OMXSTO:IRLAB_A
Irlab Therapeutics Ab Class A — Investor Day (October 2023)
67 slides from Irlab Therapeutics Ab Class A's investor day presentation, Oct 17, 2023
Slide 1: World-leader in drug development in Parkinson's
IRLAB World-leader in drug development in Parkinson’s: Reducing the burden and transforming lives Capital Markets Day October 17, 2023
Slide 2: Today's speakers
Today’s speakers Karl Kieburtz Gunnar Olsson Joakim Tedroff Peter Wallich Nicholas Waters Prof. in Neurology; CEO, IRLAB Neurologist, Commercial EVP, Head of R&D, President, co- CMO, IRLAB Director, IRLAB IRLAB founder Clintrex 2
Slide 3: Today's program
Today’s program Time Topic Speaker 14.30 Welcome & introduction Mats Thoren, Moderator 14.35 Transforming life for people living with Parkinson’s disease Gunnar Olsson, MD, CEO, IRLAB 14.45 Understanding Parkinson’s and its burden on patients, Joakim Tedroff, MD, CMO, IRLAB families, and society 14.
Slide 4: Transforming life for people living with Parkinson's disease
Transforming life for people living with Parkinson’s disease Gunnar Olsson CEO, IRLAB
Slide 5: Disclaimer
Disclaimer This document, “IRLAB Therapeutics” (the “Presentation”), has been prepared by IRLAB Therapeutics AB (publ) (“IRLAB”) and is provided for informational purposes only. All information in this Presentation has been compiled in good faith by IRLAB. Neither IRLAB nor any of its directors, emp
Slide 6: What? Why? How?
IRLAB’s… What? Why? How? • IRLAB strives to improve • 10.9 million people with • Cutting-edge expertise in the life of people living with Parkinson’s in 20221 – Parkinson’s Parkinson’s and other CNS doubling in the next 15-20 • Unique discovery platform diseases by developing new years (ISP) and bet
Slide 7: Our strategy
Our strategy • Addressing all stages of Parkinson’s disease and other CNS diseases • Discovering novel candidate drugs (CDs) with our ISP platform • True innovation • Higher success rate • Strong IP position • Developing CDs from discovery to Proof-of-Concept (PoC) • Seeking partnering after PoC 7
Slide 8: Key developments and growth of the project portfolio during 2023
Key developments and growth of the project portfolio during 2023 • Mesdopetam • Phase IIb read out – Phase III readiness • Secured full ownership and rights to the product • Pirepemat • Phase IIb study ongoing - all clinical sites opened • First pre-specified DSMB evaluation – continue according to
Slide 9: Development portfolio transforming treatment of people living with Parkinson's
Portfolio Development portfolio transforming treatment of people living with Parkinson’s Discovery Preclinical Phase I Phase IIa Phase IIb Phase III Next major event Parkinson’s disease levodopa- Phase III Mesdopetam induced dyskinesia (PD-LIDs) ready • End-of-Phase 2 (IRL790) D3 antagonist meeting
Slide 10: Parkinson's disease progresses over time – symptoms and complications expand
Parkinson’s disease progresses over time – symptoms and complications expand Initial symptoms before diagnosis Parkinson’s disease diagnosis Psychiatric Psychosis symptoms Cognitive Hallmark symptoms: impairment Apathy Hallucinations • Tremors Balance and falls Confusion Freezing when Motor • Bradyk
Slide 11: World-leading portfolio to improve treatment of Parkinson's
Parkinson’s and Parkinson’s disease World-leading progresses portfolio overthe to improve time – IRLAB’s portfolio symptoms of treatment and complications expand Parkinson’s Initial symptoms before diagnosis Parkinson’s disease diagnosis IRLAB’s portfolio with first-in- class drug candidates to trea
Slide 12: Understanding Parkinson's and its burden on patients, families, and society
Understanding Parkinson’s and its burden on patients, families, and society Joakim Tedroff, MD, PhD Consultant Neurologist, Associate Professor of Neurology and Chief Medical Officer at IRLAB
Slide 13: What is Parkinson's disease?
Parkinson’s disease What is Parkinson’s disease? What happens? Loss of >50% cells in the brain that produce dopamine Why is that important? Dopamine is one of the most important signaling substances in the brain. Controlling emotions, thoughts and movements (motor functions) Why does it happen? Age
Slide 14: The average patient is diagnosed at the age of 60
The average patient is diagnosed at the age of 60 • The average age of onset is approximately 60 years, after which the risk of disease increases significantly. • As global demographic shifts continue to increase the relative proportion of elderly populations, the social and economic burden associat
Slide 15: The Emerging Evidence of the Parkinson's Disease Pandemic
The Emerging Evidence of the Parkinson’s Disease Pandemic Dorsey et al 2018 Pandemics are usually equated with infectious diseases like Zika, influenza, and HIV,” said Dorsey. “But neurological disorders are now the leading cause of disability in the world and the fastest growing is Parkinson’s dise
Slide 16: Braak staging of Parkinson's disease
Braak staging of Parkinson’s disease Stages 5+6 The ascending pathological process within the PD brain1 Substantia nigra, Neocortex higher order association secondary) Neocortex Stage 4 (primary & Dorsal motor Mesocortex, Gain setting amygdala X nucleus thalamus nuclei Stage 3 Stage 2 1 2 3 4 5 6 Br
Slide 17: Parkinson's disease progresses over time
Parkinson’s disease progresses over time Hoehn-Yahr (H-Y) staging system Prevalence 13% 29% 34% 17% 7% Adapted from Claesson I, Better Balance with Somatosensory Exercises-a Parkinson Perspective Thesis · January 2018 17 Prevalence: Enders et al, 2017
Slide 18: Parkinson's disease progression - Quality of Life
Parkinson’s disease progression - Quality of Life Evans et al, 2011 18
Slide 19: Parkinson's disease progresses over time – symptoms and complications expand
Parkinson’s disease progresses over time –symptoms and complications expand Initial symptoms before diagnosis Parkinson’s disease diagnosis Psychiatric Psychosis symptoms Cognitive Hallmark symptoms: impairment Apathy Hallucinations • Tremors Balance and falls Confusion Freezing when Motor • Bradyki
Slide 20: Patient journey for Parkinson's patients
Patient journey for Parkinson’s patients Patients present at Primary care, then quickly referred to specialist. Diagnosis Initial Treatment Chronic Treatment Initial Presentation • Early-stage PD patients receive drug Mid to late-stage Complications Primary Care Physician therapy in 74–89% of case O
Slide 21: Strengths and limitations of gold standard anti-Parkinson treatment levodopa
Strengths and limitations of gold standard anti-Parkinson treatment levodopa Short half-life (~1 hour)1 1 Gold standard, the most effective 1 symptomatic therapy in PD4,5 Only a small percentage of oral levodopa reaches the brain1 2 Early wearing-off leading Acceptable to reduced quality of life2,3
Slide 22: Top priorities in Parkinson's disease
Top priorities in Parkinson’s disease • Systematic survey of PD • Priority # 1: Falls patients, care giver, care • Priority # 2: Stress and professionals about crucial Anxiety issues in day-to-day life. • Priority # 3: Dyskinesia • Deane et al, 2014 22
Slide 23: The Voice of the Patient
The Voice of the Patient A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative • Parkinson’s disease impacts all aspects of their lives, limiting ability to work, care for themselves and others, and to maintain relationships. • When aske
Slide 24: Market opportunities in Parkinson's and CNS
Market opportunities in Parkinson’s and CNS Peter Wallich Commercial Director, IRLAB
Slide 25: Targeting a large and growing market in Parkinson's disease
Targeting a large and growing market in Parkinson’s disease Most common neurodegenerative disorder after Alzheimer’s disease • Parkinson’s market set for expansion with approvals of pipeline drugs and improved diagnosis Expected • Reimbursement issues - common barrier 10.9 million growth to 12.4 to
Slide 26: Treatment of Parkinson's is heterogeneous with no one-size-fits-all approach
Treatment of Parkinson's is heterogeneous with a no one-size-fits-all approach Treatment of Parkinson’s Lower impact of Increased use of Deep brain motor functions adjunctive stimulation • Highly personalized approach Delay levodopa treatment due to DUOPA • Complex Dopamine agonists or monoamine oxi
Slide 27: Parkinson's disease is a dynamic and evolving market
Parkinson’s disease is a dynamic and evolving market • Mainly mature brands as Standard of Care with increasing genericization • Treatment of late-stage Parkinson’s offers greater opportunities due to the emergence of motor and non-motor symptoms • High level of pipeline activity • Slow progress and
Slide 28: Parkinson's disease pipeline target areas
Parkinson’s disease pipeline target areas Patient population Clinical utility (effect, adverse events, novel) 28
Slide 29: Parkinson's disease pipeline target areas
Parkinson’s disease pipeline target areas Patient Gut-brain Disease-modifying/ population mechanisms slowing progression (microbiome) (Alpha-synuclein, Gene, Mainly late-stage development cell therapy) LD/CD new formulations Early to late development Alternative to levodopa Motor and non- /optimizin
Slide 30: IRLAB focusing on differentiated medicines in niche segments with the greatest unmet needs
IRLAB focusing on differentiated medicines in niche segments with the greatest unmet needs Patient population Gut brain IRLAB products in development Disease-modifying/ mechanisms slowing progression IRLAB products’ potential (microbiome) LD/CD new formulations Alternative to levodopa Motor Motorand
Slide 31: IRLAB focusing on differentiated medicines in niche segments with the greatest unmet needs
IRLAB focusing on differentiated medicines in niche segments with the greatest unmet needs Patient population Gut brain IRLAB products in development Disease-modifying/ mechanisms slowing progression IRLAB products’ potential (microbiome) LD/CD new formulations Alternative to levodopa Motor and non-
Slide 32: IRLAB's mid to late-stage programs aiming for differentiated medicines
IRLAB’s mid to late-stage programs aiming for differentiated medicines in segment areas with large unmet needs Mesdopetam - Phase III ready Pirepemat - Phase IIb ongoing Dyskinesia is Good tolerability Falls represent a Anti-dyskinetic Low number of recognized as one of and safety profile major unme
Slide 33: IRLAB's commercial opportunity
IRLAB’s commercial opportunity
Slide 34: IRLAB assets targeting large market opportunity in Parkinson's disease
IRLAB assets targeting large market opportunity with high unmet need in Parkinson’s disease Improvement Alternativ PD- PD LIDs PD-Falls of Cognitive e to Parkinson’s disease Apathy Function levodopa IRLAB’s MESDOPETAM PIREPEMAT IRL757 IRL942 IRL1117 Diagnosed patients asset in 8 major markets* 7.2 m
Slide 35: IRLAB assets targeting large market opportunity in Alzheimer's disease
IRLAB assets targeting large market opportunity with high unmet need in Alzheimer’s disease Improvement of Apathy Alzheimer’s disease Cognitive Function IRLAB’s asset IRL757 IRL942 54%, 59% and 43% Diagnosed patients in 10 major markets* 11.2 million Prevalence (mild, moderate, and 27% severe dement
Slide 36: Further opportunities for mesdopetam and pirepemat will access broader populations
Further opportunities for mesdopetam and pirepemat will access broader populations IRLAB’s pipeline candidate Pipeline-in-a-Pill Life-cycle opportunities IRLAB’s pipeline candidates opportunities • Prevention of dyskinesia • Tardive dyskinesia (~ 2.3 Mesdopetam • Psychosis in Parkinson’s million pat
Slide 37: IRL757's potential to address broader populations
IRL757’s potential to address broader populations IRLAB’s pipeline candidate Pipeline-in-a-Pill Life-cycle opportunities IRLAB’s pipeline candidates opportunities • Prevention of apathy Frontotemporal dementia IRL757 (1.2 to 1.8 million worldwide Lead indication: Treatment with prevalence of Apathy
Slide 38: Commercialization strategy
Commercialization strategy Offering differentiated Partnering approach Business development new chemical entities • Focus on Parkinson’s • Awareness of IRLAB and the development • Addressing areas of high disease and/or CNS pipeline is increasing unmet need • Mid to large size • Continuous and frequ
Slide 39: Mesdopetam: treating levodopa-induced dyskinesias in Parkinson's
Mesdopetam: treating levodopa-induced dyskinesias in Parkinson’s (PD-LIDs) Nicholas Waters, MD EVP and Head of R&D, IRLAB
Slide 40: Mesdopetam (IRL790)
Mesdopetam (IRL790) Patent-based First in class- a novel Inhibiting dopamine exclusivity into the mechanism D3 receptors 2040s Lead indication – levodopa-induced dyskinesias (PD-LIDs) 40
Slide 41: Growing body of clinical evidence supporting a novel treatment of dyskinesia in PD
Mesdopetam Growing body of clinical evidence supporting a novel treatment of dyskinesia in PD Clinical studies of mesdopetam Phase IIb PD-LIDs Phase Ib Phase IIa Phase I DDI Phase I: SAD Pivotal study program Phase I HMB +MAD PD-LIDs* PD-LIDs PD-LIDs Phase I special populations • Well tolerated • We
Slide 42: Mesdopetam - Phase IIb study conclusions
Mesdopetam Mesdopetam - Phase IIb study conclusions FAS population PS population ”Good ON” UDysRS OFF-time ”Good ON” UDysRS OFF-time -12.0 • Consistent dose-response and clinically meaningful anti- • No untoward effects on normal motor functions or PD dyskinetic efficacy symptoms, i.e., no increase
Slide 43: Mesdopetam's Phase IIb results align with the endpoint structure in the amantadine ER file
Mesdopetam Mesdopetam’s Phase IIb study results align with the endpoint structure in the amantadine ER file Key efficacy endpoints FAS Nominal PS Nominal important to the FDA population P-value population P-value Primary endpoint* UDysRS part 1, 3 and 4 -6.2 ✓ 0.026 -9.2 ✓ 0.011 Key secondary endpoi
Slide 44: Mesdopetam as a solution with great potential
Mesdopetam as a solution with great potential Karl Kieburtz, MD, MPH • Professor in Neurology; President and co-founder of Clintrex • Former chairman of the Peripheral and Central Nervous System US FDA Advisory Committee • Former Chairman of the Scientific Evaluation Committee for the Cooperative St
Slide 45: Planning for a Phase III – 1/2
Planning for a Phase III – 1/2 • Critical steps with US FDA in Drug development; • Type B meetings pre-IND, End-of-Phase 2, pre-NDA • Type B meetings are live interactions with FDA staff since they occur at critical junctures • End-of-Phase 2 (EOP2) meetings are essential to reach consensus with the
Slide 46: Planning for a Phase III – 2/2
Planning for a Phase III – 2/2 • After a EOP2, it is also possible to have a Special Protocol Assessment (SPA) to get definitive agreement about the pivotal study protocol design and analysis plan. • Having a clear consensus at an EOP2, potentially with a SPA agreement, substantially decreases the l
Slide 47: A pivotal study in Parkinson's
A pivotal study in Parkinson’s • Unlike many clinical trials in CNS conditions, a pivotal trial in PD-LIDs is intended to demonstrate clinical benefit in a short time frame, in this case 12-13 weeks. Many CNS trials attempt to show slowing of clinical decline (eg most AD studies) which require up to
Slide 48: Possible evidence needed for approval
Possible evidence needed for approval • In general, the FDA requires ‘substantial evidence of efficacy’ for approval, most commonly achieved 2 pivotal studies. However, there is a strong movement within the FDA Office of Neuroscience to utilize other pathways. Although accelerated approval based on
Slide 49: Mesdopetam's clinical utility and potential
Mesdopetam’s clinical utility and potential • A treatment that both reduces dyskinesias and improves PD disability (as measured by OFF-time) is exceedingly rare. • Only Gocovri has FDA approval for this unusual combination of features • Most drugs can produce one or the other effect, usually mildly
Slide 50: Pirepemat: Reducing falls in Parkinson's
Pirepemat: Reducing falls in Parkinson’s Joakim Tedroff, MD, PhD Consultant Neurologist, Associate Professor and Chief Medical Officer at IRLAB
Slide 51: Falls in Parkinson's disease
Pirepemat Falls in Parkinson’s disease Reducing falls is the greatest medical need and one of the worst aspects of Parkinson’s. • Prospective studies report that 70% of people with Parkinson’s have at least one fall in a year and about 45% fall recurrently. • Median survival in patients that have re
Slide 52: Clinical development path for pirepemat
Pirepemat Clinical development path for pirepemat: Improvement of balance and falls Completed Ongoing Planned Phase IIa Phase IIb Phase I: SAD+MAD PD-cortical Pivotal studies PD-Falls impairment o Evaluate the effects on Parkinson's motor function ü Well tolerated ü Well tolerated as compared to pla
Slide 53: Pirepemat Phase IIa in Parkinson's – postural function
Pirepemat (IRL752) Phase IIa in Parkinson’s – postural function Pirepemat improves Parkinson’s ~50% reduction in falls symptoms not treated by levodopa 0,6 1 0,4 0,2 0 IRL752 Placebo -0,2 -0,4 -0,6 -0,8 -1 -1,2 -1,4 ** Mean absolute from baseline (with 95% conf. Intervals) in the four cardinal PD mo
Slide 54: Pirepemat Phase IIa in Parkinson's – executive function
Pirepemat (IRL752) Phase IIa in Parkinson’s – executive function Pirepemat significantly improve executive function One Touch Stockings of Cambridge Median Mean (SD) Parameter baseline End of baseline End of Ttrt Ttrt First Higher 3 4.5 3.9 (4.0) 4.9 (3.0) choice better accuracy Latency to Lower 3.9
Slide 55: Phase IIb study evaluating pirepemat on falls frequency: study design
A randomised, placebo-controlled, multi-centre Phase IIb study evaluating the efficacy of pirepemat on falls frequency in patients with Parkinson´s disease Study design of IRL752C003 6 weeks Dose Dose 33-37 days escalation 12-week treatment period follow up screening De-escalation n=55 Pirepemat 300
Slide 56: IRL752C003 / REACT-PD Phase IIb study status
IRL752C003 / REACT-PD A randomised, placebo-controlled, multi-centre Phase IIb study evaluating the efficacy of pirepemat on falls frequency in patients with Parkinson´s disease Status • Study start of Phase IIb - Q1 2022 • All clinical centers activated - May 2023 • 38 centers in France, Poland, Sp
Slide 57: Preclinical projects and generating a pipeline with ISP
Preclinical projects and generating a pipeline with ISP Nicholas Waters EVP, Head of R&D at IRLAB
Slide 58: Preclinical projects in development
Preclinical Preclinical projects in development projects IRL757* IRL942* IRL1117 Treatment for Improvement of cognitive Once-daily treatment of apathy function Parkinson’s (tremor, rigidity, bradykinesia) without treatment- related complications Loss of initiative, interest, and Memory, perception,
Slide 59: Pipeline generated with our proprietary drug discovery platform - ISP
ISP Pipeline generated with our unique proprietary drug discovery platform - ISP Integrative Screening Process (ISP) • Advanced systems biology approach • Drug design informed by machine learning techniques • ISP predicts drug candidates with greatest benefit potential and lowest toxicity risk, base
Slide 60: ISP gives an advantage through increased probability of development success
ISP gives an advantage through increased Research platform ISP probability of development success Discovery and Estimated overall preclinical transition from CD Phase I to Phase III Probability with Phase II 50% 80% 50% ISP %* Phase III 20% Probability according 7% to industry standard %** 35% 63% 3
Slide 61: Panel discussion on regulatory strategy and business development
Panel discussion with a focus on regulatory strategy and business development opportunities
Slide 62: Biogen and Alectos license and collaboration agreement in Parkinson's Disease
Biogen and Alectos announce license and collaboration agreement in Parkinson’s Disease + = Deal Value: Up to USD 722.5m • Exclusive global license Transaction • Collaboration on preclinical activities. Biogen assumes sole responsibility for clinical development, regulatory, manufacturing and commerc
Slide 63: Takeda and Ovid Therapeutics license agreement
Takeda and Ovid Therapeutics announce license agreement with respect to Seizure Control in DS and LGS + = Deal Value: Up to USD 856m • Exclusive global license Transaction • Takeda assumes sole responsibility for clinical development, regulatory and commercial activities and costs • Soticlestat – a
Slide 64: Jazz Pharmaceuticals acquisition of Cavion
Jazz Pharmaceuticals announces acquisition of Cavion with activities in Movement Disorders + = Deal Value: Up to USD 312.5m • Acquisition (global rights) Transaction • Privately held target company • CX8998 – a modulator of T-type calcium channels as a potential treatment of Essential Tremor (+ Targ
Slide 65: Supernus acquisition of Adamas
Supernus announces acquisition of Adamas with activities in e.g. Parkinson’s Disease LIDs + = Deal Value: Up to USD 450m • Acquisition (global rights) Transaction • Listed target company • GOCOVRI – extended release capsules of amantadine as a treatment for PD LIDs and PD OFF Target Epsiodes (+ Osmo
Slide 66: Questions from the audience
rm | TIRLAB It Questions from the audience
Slide 67: Contact
Contact: Gunnar Olsson, CEO, gunnar.olsson@irlab.se General enquiries: ir@irlab.se IRLAB is discovering and developing a portfolio of transformative therapies targeting all stages of Parkinson’s disease. The company has its origin in Nobel Laureate Prof. Arvid Carlsson’s research group and the disco