Irlab Therapeutics Ab Class A · OMXSTO:IRLAB_A
Irlab Therapeutics Ab Class A — Investor Day (March 2022)
84 slides from Irlab Therapeutics Ab Class A's investor day presentation, Mar 22, 2022
Slide 1: Transforming life for people with Parkinson's disease
Slide 2: 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 3: Welcome and Introduction
Welcome and Introduction Moderator Mats Thoren 20 years in life science banking and investing, board member in four listed Nordic healthcare companies r= | I RLAB Sidfot It
Slide 4: A world-leading developer of innovative drugs for Parkinson's disease
A world-leading developer of innovative drugs for the treatment of Parkinson’s disease and other disorders of the brain m7 IRLAB it
Slide 5: Validation of strategy towards vision
Validation of strategy towards vision . Published in high ranked publications Science Recognition by independent well established scientists (2017 and onward) Translation with high success rate Successful clinical proof of concept for both mesdopetam and pirepemat (2019) Innovation/Novelty New drug
Slide 6: Well positioned to deliver
Well positioned to deliver * Two “first in class” programs in late-stage Clinical Phase IIb + Addressing large global markets * Partnership with Ipsen - a leading global neuroscience company * Preclinical development candidates towards clinical Phase | * Highly efficient discovery platform for “firs
Slide 7: Strong momentum in operations
Strong momentum in operations ° Well ahead of competition * Mesdopetam fully financed through Phase III and marketing * Strong cash position * Strong newsflow 2022-2024 = TRLAB It
Slide 8: Pipeline generated by our unique proprietary technology platform: ISP
Pipeline generated by our unique proprietary technology platform: ISP ISP — next level drug discovery * Advanced systems biology interlinked with drug design and machine learning (ML, Al) techniques Results in * Discovery of novel “first in class” compounds * Strong IPR ° Predictive science for use
Slide 9: Performance statistics: ISP vs industry
Performance statistics CD to PhI PhI to PhII PhII to PhIII Estimated overall transition CD to Phase III ISP – percentage* 50 % 80 % 50 % 20 % Industry – percentage** 35 % 63 % 30 % 7% * Based on ISP-generated “first in class” candidate drugs from 2000. NB, small sample size. ** Based on Paul et al,
Slide 10: Pipeline overview
PRE DISCOVERY PHASE I PHASE IIa PHASE IIb PHASE III CLINICAL MESDOPETAM (IRL790) D3 antagonist MESDOPETAM (IRL790) D3 antagonist PIREPEMAT (IRL752) PFC Enhancer PIREPEMAT (IRL752) PFC Enhancer IRL942 IRL757 P003 - Dopamine substitution
Slide 11: Path to deliver strong growth
Path to deliver strong growth Foundation Building Delivering for transformative treatments for the future first-in-class treatments 2020 - 2023 2023 - 2025 2025 - 2027 Mesdopetam Mesdopetam Mesdopetam Successful completion of Phase IIb/III Phase III studies initiated with partner Finalizing Phase II
Slide 12: Upcoming newsflow 2022-2024
2022 Mesdopetam Phase IIb LIDs TLR** Pirepemat Ilb FPFV* IRL942 through preclin dev IRL757 through preclin dev POO3 first CD Upcoming newsflow 2022-2024 2023 Pirepemat Phase IIb Top Line Res IRL942 Phase | FPFV * IRL942 phase 1TLR IRL757 Phase | FPFV * IRL757 phase | TLR POO3 CD Phase | FPFV Mesdope
Slide 13: Parkinson's disease stages
Parkinson’s disease stages Early stage Complicated stage Late stage HY 0-2.5 HY 3-4 HY 5 c € m “+ Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Prevalence 13% 29% 34% 17% 7% ial LRLAB + Adapted from Claesson I, Better Balance with Somatosensory Exercises-a Parkinson Perspective Thesis - January 20
Slide 14: No more falls, promoting brain health, optimal treatment
No more falls Promoting brain health Optimal treatment with levodopa without LIDs or psychosis Once daily - normal motor function without complications 14
Slide 15: Q&A
Q&A
Slide 16: Partnering with IRLAB
Te IRLAB Partnering with IRLAB Stephen Glyman Senior Vice President and Head of Neuroscience Therapeutic area at Ipsen + Currently in development with partner Ipsen who holds an exclusive global license to develop and commercialize mesdopetam + (https://www.irlab.se/press-releases/ipsen-and-irlab-en
Slide 17: Ipsen-IRLAB
Ipsen-IRLAB March 2022 PAGE 17
Slide 18: About Ipsen
About Ipsen Our mission We are dedicated to prolonging and improving patients’ lives and health outcomes. Our vision To be a leading global, mid-sized biopharmaceutical company with a focus on transformative medicines in Oncology, Rare Disease & Neuroscience. PAGE 18
Slide 19: Our key figures
Our key figures 25+ Medicines in over €2.9bn 100 countries 2021 Group sales 5,700+ Colleagues worldwide up by +12.3%1 In 2021, Ipsen invested 7 Manufacturing facilities €428.4m 4 Global R&D hubs: Paris-Saclay, France; Oxford, U.K.; Cambridge, U.S.; Shanghai, China in R&D, equivalent to 14.9% of sale
Slide 20: Bolstering an innovative pipeline
Bolstering an innovative pipeline Our pipeline is driven by external innovation. We encourage open innovation through trusted partnerships with biotech and academic institutions. Our pipeline includes innovative new molecules, including small molecules and Ipsen 2019 / Adam Wiseman / CAPA Pictures n
Slide 21: Partnerships focused on our key pillars
Partnerships focused on our 3 key pillars Accelerated external innovation efforts to build a high-value sustainable pipeline: Focus on assets across all stages of development Oncology Rare Disease Neuroscience • Solid & hematological tumors • Disease areas with unmet • Focus on in-house • Niche tumo
Slide 22: Why mesdopetam for Ipsen?
Why mesdopetam for Ipsen? © Ipsen 2019 / Adam Wiseman / CAPA Pictures Matt & Suzanne Scientific Intelligence dpt. & Communication dpt. Milton Park, UK PAGE 22
Slide 23: IRLAB's mesdopetam: Fit with Ipsen's Neuro Strategy
IRLAB’s mesdopetam: Fit with Ipsen’s Neuro Strategy ▪ Novel mechanism of action with strong scientific rationale ▪ Dopamine D3 receptor has been demonstrated in preclinical studies (e.g., knock-out studies) to be involved in the development of levodopa-induced dyskinesia (LID). The results of the Ph
Slide 24: Follow us
Follow us www.ipsen.com ALL-ALL-004381 PAGE 24
Slide 25: Q&A
Q&A
Slide 26: Mesdopetam (IRL790)
Te IRLAB Mesdopetam (IRL790) ¢ Improve motor function through prevention and reduction of dyskinesias (LIDs) ¢ Treatment and prevention of psychosis in Parkinson’s (PD-P) ¢ Potential opportunity in TD arkinsons-disease, + Currently in development with partner Ipsen who holds an exclusive global lice
Slide 27: Living with Parkinson's: IRLAB transforms the treatment algorithm
Living with Parkinson’s: IRLAB transforms the treatment algorithm Before diagnosis Parkinson's diagnosis Balance/falls Cognitive Apathy impairment; Dyskinesia Psychosis T T T T -20 yrs -10 yrs Oyrs 10 yrs 20 yrs > Approximate onset of symptom References: Based on Kalia, LV. and Lang, AE. Lancet * Cu
Slide 28: Important motor and non-motor outcomes in PD
Important motor and non-motor outcomes in PD Karl Kieburtz MD MPH Professor of Neurology University of Rochester School of Medicine President, Clintrex LLC
Slide 29: Major PD disability occurs late in the clinical course
Major PD disability occurs late in the clinical course: Motor fluctuations and Hallucinations are common, and are worsened (or unaided) by current therapies
Slide 30: CALM PD: Pramipexole vs. Levodopa as Initial Treatment
CALM PD:Pramipexole vs. Levodopa as Initial Treatment for PD Demonstrated that 50% of treated PD have motor complications by 2 years Percentages of patients experiencing dopaminergic complications first dopaminergic complication wearing-off dykinesias PSG JAMA 2000; 284:1931-1938
Slide 31: Eventually, most of the day is 'Bad time'
Eventually, most of the day is ‘Bad time’- ‘off’ or ‘on’ with troublesome dyskinesias: DBS helps (medication does not), but invasive with significant morbidities JAMA. 2009;301(1):63-73. doi:10.1001/jama.2008.929
Slide 32: Intestinal infusion helps fluctuations, but still invasive
Intestinal infusion (perhaps SQ now) helps fluctuations, but still invasive Unlike DBS, little observed impact on troublesome dyskinesias
Slide 33: OFF time reduction with available oral adjunctive treatment
OFF time Reduction Approximately an Hour with available oral Adjunctive Treatment- modest effects
Slide 34: Amantadine can decrease dyskinesias
Amantadine can decrease dyskinesias, and thereby increase ‘good on time’- on without troublesome dyskinesias- but many PD patients do not tolerate an adequate dosage, in part due to mental side effects
Slide 35: Hallucinations are a dosage limiting problem in PD treatment
Hallucinations are a dosage limiting problem in PD treatment The only available treatment can work well, in a subset of PD Restoring Movement with Ease
Slide 36: PD Patients Continue to Have Persistent Motor Fluctuations and Hallucinations
PD Patients Continue to Have Persistent Motor Fluctuations and Hallucinations Despite Current Medical Options Representing Significant Unmet Needs • Off time persists despite available treatments • 2.3 hours OFF time at 12 weeks despite double-dummy optimal titration of duopa • Rytary end of study:
Slide 37: Q&A
Q&A
Slide 38: Mesdopetam - Market opportunity in the largest markets (8MM)
Mesdopetam - Market opportunity in the largest markets (8MM) (US, DE, UK, FR, ES, IT, CH, JP) 235,000 LID population 1.0 million 196,000 PD-P population 1.4 million 329,000 Total population eligible for mesdopetam within PD 2.4 million patients There might be an overlap between patients with LID and
Slide 39: Mesdopetam - Market opportunity
Mesdopetam - Market opportunity Total population eligible for mesdopetam within PD is about 2. 4 . es atie nts a Peer prices 2021 ElRs about ( Estimated pricing based on market data - ew oh USD 30, 000 per year in the US in both LIDs and PD-P | Addressable LID market (USD) — (Amantadin for PD-LIDs a
Slide 40: Mesdopetam - Market opportunity (TD)
Mesdopetam - Market opportunity Peer prices 2021 are about USD 45,000 per year in Diagnosed TD population 434,000 the US | ( 10 population 2.2 million (Using data for Austedo with Ingrezza being even ( Racca etacecelen ute higher) ane ( Addressable TD market (USD) Total addressable market for mesdop
Slide 41: Pirepemat (IRL752)
Te IRLAB Pirepemat (IRL752) Improve balance and reduce falls in Parkinson’s (PD-Falls)
Slide 42: Parkinson's disease stages
Parkinson’s disease stages • •
Slide 43: Living with Parkinson's: IRLAB transforms the treatment algorithm
Living with Parkinson’s: IRLAB transforms the treatment algorithm Before diagnosis Parkinson's diagnosis Balance/falls Cognitive Apathy impairment; Dyskinesia Psychosis Bradykinesia Rigidity. Tremér T T T T -20 yrs -10 yrs Oyrs 10 yrs 20 yrs ‘Approximate onset of symptom References: Based on Kalia,
Slide 44: Balance and falls in Parkinson's disease
Balance and falls in Parkinson’s disease Professor Bas Bloem Centre of Expertise for Parkinson & Movement Disorders Radboud University Medical Centre @BasBloem
Slide 45: Postural reflexes in 1994
Postural reflexes in 1994 ( I ) Parkinson’s disease w pe) n D cf se) i) 5 a w Ss fo) g 5
Slide 46: March 21, 2022 (!)
\cceptance of Interventions for preventing falls in Parkinson's dis fou are being carbon copied ["cc‘'d"] on an e-mail "To" "Callen G Canning" colleen.canning@aydney.edu.au schrane.org, covelman@cochrane.org, "Natalie Allen” natalie. allen@sydney.edu.au, "Lorena Rosa Almeida slice.nieuwboer @faber-k
Slide 47: Impact of falls
Impact of falls
Slide 48: Is falling an issue in Parkinson disease?
Is falling an issue in Parkinson disease? Bloem et al., Mov Disord 2004;19:871-884
Slide 49: Falls are a 'late' feature in Parkinson's
Falls are a “late” feature in Parkinson’s Risk of falls (in subjects with no prior falls) 0.6 0.4 0.2 0.0 0 20 40 60 80 UPDRS score Pickering et al., Mov Disord 2007;22:1892-1900
Slide 50: Fear of falls in Parkinson disease
Fear of falls in Parkinson disease Percentage with fear 80 70 P < 0.05 60 50 40 30 20 10 0 Recurrent Non- fallers fallers Bloem et al., J Neurol 2001;87:950-958
Slide 51: Injuries in Parkinson disease
Injuries in Parkinson disease Hip fracture Epidural hematoma
Slide 52: Home-Based Monitoring of Falls Using Wearable Sensors
RESEARCH ARTICLE Home-Based Monitoring of Falls Using Wearable Sensors in Parkinson’s Disease Ana Ligia Silva de Lima, PhD," Tine Smits, MSc,? Sirwan K. L. Darweesh, MD, PhD,":** Giulio Valenti, PhD,” Mladen Milosevic, PhD,° Marten Pijl, PhD,? Heribert Baldus, PhD,? Nienke M de Vries, PhD,’ Marjan J
Slide 53: Automated falls detection
Automated falls detection • 3 linear accelerometers • 1 height sensor • Algorithms validated (?)
Slide 54: Connection to help desk
Connection to help desk Fall at home Telephone help desk
Slide 55: Documented falls (top conditions)
Documented falls (top 12 conditions) • Red: self-report on device without sensors (button press after fall) • Green: device with sensors – Dark green: self-report (button press after fall) # falls/year – Light green: automated falls detection • All falls presented were confirmed by a call 700.000 da
Slide 56: Risk of first fall
Risk of first fall Probability of remaining free from falls Time (days)
Slide 57: Parkinson's disease is the number 1 falling disorder
“Take home” message! Parkinson’s disease is the number 1 falling disorder
Slide 58: Causes of falls
Causes of falls
Slide 59: Causes of falls: environment, postural instability, gait, cognition
= patient-related (“intrinsic”) = outside the patient (“extrinsic”) Environment Postural Gait FALLS instability impairment Cognitive decline
Slide 60: Also common in COGNITIVE disorders
Also common in COGNITIVE disorders
Slide 61: Falls are common in dementias
Falls are common in dementias
Slide 62: Perhaps even particularly cognitive?
Perhaps even particularly cognitive? Severity (in Parkinson’s disease) Gait impairment & postural instability Hypothesis Compensatory mechanisms Cognitive impairment Falls and injuries Time
Slide 63: Multiple tasking and falls in PD
Multiple tasking and falls in PD Percentage P = 0.001 80 70 60 50 40 30 20 10 0 Patients Controls Bloem et al, J Neurol 2001;87:950-958
Slide 64: The 'posture second' strategy
Journal of the Neurological Sciences - foe ELSEVIER Journal of the Neurological Sciences 248 (2006) 196 — 204 www.clsevier.com/locate/jns The “posture second” strategy: A review of wrong priorities in Parkinson’s disease Bastiaan R. Bloem**, Yvette A.M. Grimbergen °, J. Gert van Dijk ®, Marten Munne
Slide 65: Avoid benzodiazepines!
Avoid benzodiazepines! With benzodiazepines No benzodiazepines RR 5.0 (P < 0.01) Benzodiazepines Bloem et al., J Neurol 2001;248:950-958
Slide 66: Example of falling due to freezing
Example of falling due to freezing
Slide 67: Treatment of gait & balance / prevention of falls
Treatment of gait & balance / prevention of falls
Slide 68: Clinical state in relation to falls
Clinical state in relation to falls Dopaminergic Dopa-induced abnormalities abnormalities Non- dopaminergic abnormalities
Slide 69: Clinical state in relation to falls
Clinical state in relation to falls Increase levodopa Dopaminergic Dopa-induced abnormalities abnormalities “OFF” period freezing Non- dopaminergic abnormalities
Slide 70: Clinical state in relation to falls
Clinical state in relation to falls Decrease levodopa Decrease agonist Dopaminergic Dopa-induced abnormalities abnormalities Non- “ON” period freezing dopaminergic abnormalities
Slide 71: Clinical state in relation to falls
Clinical state in relation to falls Dopaminergic Dopa-induced abnormalities abnormalities Idazoxan? Non- dopaminergic L-threo-DOPS? “Non-dopaminergic” abnormalities Methylphenidate freezing? Duloxetine Pirepemat
Slide 72: THANK YOU!
THANK YOU!
Slide 73: Pirepemat Phase IIb: Impaired balance/Falls
Pirepemat Phase IIb: Impaired balance/Falls Primary objective in study IRL752C003 Effects on falls frequency Secondary & other objectives 7 + Effects on cognitive functions (Montreal Cognitive A P h ase | | b stu dy to Secon Nese) evaluate the effects of * Effects on Parkinson's disease symptoms (MD
Slide 74: Q&A
Q&A
Slide 75: Pirepemat — Market opportunity
Pirepemat — Market opportunity 489,000 USD 24k ( ®0 population 4.7 million 939,000 [ *Recurrentfallers’ (89%) 1.9 million ( Potential pricing* _— ( Addressable PD-Falls market (USD) Total addressable market for pirepemat is about USD 30 bn ial LRLAB Source: Global Data 2020. Europe represented by “E
Slide 76: Preclinical portfolio to accelerate IRLAB's growth
Te IRLAB Preclinical portfolio to accelerate IRLAB’s growth IRL942 and IRL757: To improve cognitive function, brain health and treat apathy (target populations: PD, dementias, schizophrenia, depression) POO3: Long-acting Parkinson treatment with better efficacy than L-DOPA or apomorphine and reduced
Slide 77: Living with Parkinson's: IRLAB transforms the treatment algorithm
Living with Parkinson’s: IRLAB transforms the treatment algorithm Before diagnosis Parkinson's diagnosis Balance/falls Cognitive Apathy impairment Dyskinesia Psychosis Bradykinesia Rigidity Tremor T T T T -20 yrs -10 yrs Oyrs 10 yrs 20 yrs ‘Approximate onset of symptom References: Based on Kalia, LV
Slide 78: IRL942 - Aimed at improving cognitive function and brain health
IRL942 - Aimed at improving cognitive function and brain health across neurological indications IRL942 opportunity * 12 % of adults aged 65 years or more experience cognitive decline (CDC) Problem * Disruption of frontal-subcortical circuits are implicated in the pathogenesis of cognitive decline* I
Slide 79: IRL757 - Aimed at the huge untreated problem with apathy
IRL757 - Aimed at the huge untreated problem with APATHY IRL757 opportunity * Over 10 million US and EU citizens each may be affected by apathy * Apathy occurs in 20-70% in people with PD and In 20- 90% of people with AD and other CNS disorders Pathophysiological background * Disruption of frontal n
Slide 80: P003 - Therapeutic response
• • • • • Current standard-of-care (L-DOPA) P003 objective Excessive Therapeutic response response • Optimal • response Response absent Time * Source: Global Data Epidemiology data base
Slide 81: Q&A
Q&A
Slide 82: Well positioned to deliver
Well positioned to deliver * Two “first in class” programs in late-stage Clinical Phase IIb + Addressing large global markets * Partnership with Ipsen - a leading global neuroscience company * Preclinical development candidates towards clinical Phase | * Highly efficient discovery platform for “firs
Slide 83: Strong momentum in operations
Strong momentum in operations ° Well ahead of competition * Strong cash position * Mescopetam fully financed through Phase III and marketing * Strong newsflow 2022-2024 = TRLAB It 83
Slide 84: IRLAB contact
Ball IRLAB Contact: Nicholas Waters, CEO, nicholas.waters@irlab.se, Viktor Siewertz, CFO, viktor.siewertz@irlab.se IRLAB discovers and develops novel treatments of Parkinson’s disease and other disorders of the brain. The company's most advanced drug candidates, mesdopetam (IRL790) and pirepemat (IR