Orphazyme

Pioneering the response for neurodegenerative orphan diseases

1 Company Update – April 2020 Important notice

This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, such as statements regarding our future results of operations and financial position, including our business strategy, prospective products, availability of funding, results, product approvals and regulatory pathways, collaborations, timing and likelihood of success, plans and objectives of management for future operations, and future results of current and anticipated products, are forward-looking statements. These forward-looking statements are based on our current expectations and beliefs, as well as assumptions concerning future events. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially from the results discussed in the forward- looking statements. Any forward-looking statement made by us in this presentation speaks only as of the date of this presentation and represents our estimates and assumptions only as of the date of this presentation. Except as required by law, we assume no obligation to update these statements publicly, whether as a result of new information, future events or otherwise after the date of this presentation. Orphazyme is a trademark that we own. Other trademarks appearing in this presentation are the property of their respective holders.

2 Significant progress in 2019 and early 2020

Clinical Clinical Regulatory / Access Company –Reported positive data –Breakthrough Therapy –Raised ~$110M in Feb. 2020 from phase 2/3 trial with Designation granted NPC –Expanded senior management arimoclomol in NPC –Pre-filing meetings with FDA team focused on commercial –Enrolment completed in –Initiated Early Access phase 2/3 sIBM, phase 3 Program in US in NPC ALS and phase 2 PoC –Fast Track designation Gaucher trial granted in sIBM

✓Arimoclomol in Niemann-Pick disease Type C getting closer to patients ✓ Pipeline advancing with trials in additional indications underway ✓ Team and capital resources in place to execute

3 Pro-actively addressing challenges of Covid-19

Regulatory Clinical

Preparing to submit marketing applications in Letter to investigators and patient organizations the US and EU for NPC as planned Scale up of patient-forward approaches • Home nursing service • Reimbursement Patients • Direct to patient study drug shipments Virtual data monitoring and scientific steering US Early Access Program in NPC continues as committee meetings planned Protocol addendum • Flexibility on use of local laboratories • Adjustment to visit schedule Employees • Patient observation / assessment by phone Working from home arrangements for all staff Drug supply Shift work for laboratory staff required to attend • Provide patients with sufficient drug for study company premises completion

4 Arimoclomol: Potential game-changer for neurodegenerative diseases

Protein aggregates - First-in-class heat shock protein (HSP) amplifier Protein degradation

Folded & Nascent functional HSPs are a natural cellular stress defense mechanism protein protein

Small molecule, oral/nasogastric, crosses BBB

Lysosome Favorable safety profile observed to date in >540 patients

Misfolding

5 Arimoclomol: prolific late stage pipeline focused on neurodegenerative diseases

Designations Break- Key Orphan Fast through Neuropathic lysosomal diseases Drug Track Therapy milestone Submit Niemann-Pick disease type C* Ph 2/3 (data reported) US H1 2020/ ✓ ✓ ✓ Europe H2 2020 Ph 2 results Ph 2 Neurological Gaucher disease H1 2020

GCase-Parkinson’s disease** Pre-clinical

Neuromuscular disorders

Ph 2/3 results Sporadic inclusion body myositis Ph 2/3 ✓ ✓ H1 2021 Ph 3 results Amyotrophic lateral sclerosis Ph 3 ✓ H1 2021

6 *Rare Pediatric Disease Designation (RPD) for arimoclomol in NPC **Arimoclomol / NME; glucocerebrosidase (Gcase) NPC: addressing high unmet patient and physician needs in an attractive ultra-orphan market

WW: ~ 3,000 patients Market opportunity

US/EU: ~ 1,000 patients Price range WW sales diagnosed & treated 300K - 600K MPS I: 100M USD USD/year Current estimate: only ~ 40% MPS VI: 350M USD diagnosed MPS II: 600M USD

Managed in highly Lack of current Rx/competitors specialized centers

US: no approved Rx ~ 25-50 centers in US and EU Specialist pediatric neurologists EU: generic miglustat only Specialist metabolic centers

7 Key focus: get to approval, get to patients

US EU RoW Regulatory • March 2020: BTD meeting • H1 2020: Pre-submission meeting with EMA filing • Q2’ 20: pre-NDA meeting H2 2020: Pre-submission meeting • US submission H1’ 20 • with rapporteur and co-rapporteur • Covid-19 mitigation plan in place • H2 2020: MAA Submission

Patients • ~ 300 patients diagnosed • >700 patients diagnosed • ~ 400 patients diagnosed • Early Access program since Jan • Early Access Programs focused on • Early Access Programs where 2020 France via ATU and Italy via Law possible 643 • Patient group collaboration

Physicians • US thought-leader advisory board • European KOL Advisory Board Q3/Q4 2020 • Build medical education program

Company • US President appointed • Focus on key EU markets • Finalize partnering for key especially Germany & France countries: Japan, Canada, Turkey • Building Medical Affairs and MSL teams • Build lean in-country and cluster organization • Building Market and Patient Access capabilities

8 US Early Access Program for NPC is now operational

Feb Feb Mar Jan May 14th 24th 14th

Dedicated Protocol Sites agreed Protocol live, GOAL: First US program submitted budget and posted to patient on to FDA protocol sent clinicaltrials.gov treatment

Boston Children’s Mayo Clinic Hospital- ~45 patients already Rush NYU Children’s under consideration for UCSF/Benioff Children’s Hospital Children’s Hospital Philadelphia EAP before sites are open Oakland Cincinnati Children’s Hospital Pittsburgh Children’s Hospital Emory Orange University 50% pediatric County 50% adult

9 Arimoclomol in NPC: unlocking huge potential in neurodegenerative orphan diseases

Neurological Gaucher I & III / sIBM / ALS GCase PD • Neurological Gaucher I & III: NPC • sIBM and ALS in pivotal trials • Ph 2 results H1 2020 • No current effective disease- • Filing preparations ongoing modifying Rx • GCase PD: PoC evaluation • US EAP roll out • Significant market potential • NME: Next gen HSP amplifier • Lean go-to-market strategy • No approved Rx in US

Neurodegenerative market potential market Neurodegenerative ~ 3K patients ~ 100K patients ~ 500K patients

2020+ 2022+ 2025+ Phased neurodegenerative platform 10 Orphazyme at a glance

2019 Financials Capital Increase 2020 Outlook

R&D expense: February 2020 Operating loss1: 1 ~USD 43M USD Raised gross 74M USD – 82 M USD Year-end cash: proceeds of Year-end cash1: ~18M USD1 ~ 110M USD > 45M USD

Footprint Shareholders2 Analysts

HQ Copenhagen, DK LSP (10.0%) Carnegie Boston, US Novo (7.5%) Danske 3 Zug, Switzerland Consonance (7.0%) Sunstone (6.7%) Oddo Nasdaq Copenhagen Aescap I (6.5%) Redeye ORPHA.CO

1R&D spend DKK 285.4M; year-end cash 2019: DKK 123.6M; Outlook operating loss 2020: DKK 500-550M; Outlook year-end cash 2020: >DKK 300M; USD figures 11 are for reference only; FX rate 1 DKK / 0.15 USD; 2major shareholders per recent disclosures, figures rounded, 3Consonance Capman GP LLC. Key priorities and anticipated milestones

Get to approval in NPC Submit NDA in US H1 2020

Submit MAA in EU H2 2020

Get to patients in NPC US early access program (EAP) roll-out 2020

Preparations for US launch 2020

Lean go-to market rollout US 2020

Lean go-to market roll out EU/ROW H2 2020 - 2021

Expand beyond NPC Gaucher disease Ph 2 results H1 2020

sIBM Ph 2/3 results H1 2021

ALS Ph 3 results H1 2021

12 NDA: new drug application; MAA: marketing authorization application Niemann-Pick disease type C

Clinical overview

13 NPC is an ultra-rare, devastating genetic disorder: a life-limiting condition with high unmet need

• An ultra-orphan disease • Epidemiology incidence: 1/100,000 live-births • ~ 2,000 patients across US and EU • A progressive lysosomal storage disorder characterized by the US EU accumulation of lipids • Affects cells of the brain, liver, spleen and lungs

• Loss of 5 domains: ambulation, fine motor skills, swallowing, cognition, speech

• When diagnosed in childhood, unlikely to survive beyond teenage years • ~ 300 patients diagnosed • ~ 600 patients diagnosed • Managed in ~ 25-50 and treated in EU • Adult-onset NPC is increasingly diagnosed specialist centers by • Centralized approach to pediatric neurologists patient management: • No approved treatment ~ 25-50 metabolic centres • Only approved treatment is miglustat (used in 80% of patients)

14 Arimoclomol clinical development in NPC

Oct 2015 – May 2017 Jun 2016 – Jun 2018 Jun 2017 – Dec 2019 NPC-001: observational study NPC-002: phase 2/3 study NPC-002 1 year blinded + 1 year 36 patients enrolled: 31 completed – of these, 50 patients enrolled: 42 completed – 34 treated 41 enrolled from core study: interim of 35 27 continued to NPC-002 with arimoclomol, 16 with placebo completed (1 year blinded + 1 year OLE)– 22 on continuous arimoclomol, 13 with placebo–arimoclomol

Trial design Inclusion/exclusion Key endpoints

• NPC 1/2 patients, n = 50 Inclusion Primary • 12 months + 1 year OLE • NPC 1/2 patients 2–18 years • 5-domain NPC-CSS (ambulation, fine motor skills, swallowing, speech and cognition) • 2:1 arimoclomol to placebo • Minimum 1 neurological symptom • Ability to walk with assistance Co-primary (US only) • Arimoclomol max. 200 mg t.i.d. (bodyweight dosed) • If on miglustat, stable for 6 months • CGI-I, only 8/50 patients with baseline assessment • Routine care permitted, incl. miglustat allowed Exclusion Biomarkers • Participation in other trials • HSP70, oxysterols, unesterified cholesterol • Epilepsy, liver/renal insufficiency Subgroup analyses • Patients ≥ 4 years • Routine miglustat • Excluding double functional null mutations (post hoc analysis upon FDA request)

15 15 63% reduction (observed) in disease progression after 12 months with arimoclomol versus placebo

BIOMARKERS CHANGE FROM BASELINE TO 12 MONTHS 5-domain NPC-CSS Change from baseline

• Mean treatment difference of -1.34 (95% CI - Arimoclomol, n = 34 Increasing NPC 2.71 to 0.02; p = 0.0536) in 5-domain NPC-CSS Placebo, n = 16 severity score in favor of arimoclomol versus placebo

• Considered meaningful by clinicians, and individualsFAVORABLE with NPC and SAFETY caregivers PROFILE

• Corresponds to a 63% reduction (baseline adjusted, same as observed) in disease progression

• Significance not reached owing to individuals with double functional null mutations (n = 3) in arimoclomol treatment group

16

34

16 16 80% reduction (observed) in disease progression when individuals with double functional null mutations are excluded

BIOMARKERS DOUBLE FUNCTIONAL NULL MUTATIONS 5-domain NPC-CSS Change from baseline • Presence of double functional null mutations are rare in individuals with NPC and strongly predictive Increasing NPC Arimoclomol, n = 31 of early-onset and rapid disease progression severity Placebo, n = 16 • Post hoc analysis excluding individuals with double functional FAVORABLEnull mutations SAFETY (n = PROFILE 3) in arimoclomol treatment group

CHANGE FROM BASELINE TO 12 MONTHS

• Significant mean treatment difference of -1.56 (95% CI -2.90 to -0.21; p =0.024) in 5- domain NPC-CSS score in favor of arimoclomol vs

16 placebo 31 • Corresponds to 77% reduction (baseline adjusted) in disease progression

17 17 Arimoclomol has a benefit over standard of care 95% reduction (observed) in disease progression

5-domain NPC-CSS Change from baseline SUBGROUP ANALYSIS – BACKGROUND TREATMENT Arimoclomol, n = 26 Increasing NPC • Arimoclomol treatment benefit in individuals Placebo, n = 13 severity with miglustat as background treatment (39 of 50 patients)

CHANGE FROM BASELINE TO 12 MONTHS

• Significant mean treatment difference of -2.01 (95% CI -3.44 to -0.58; p = 0.0073) in 5- domain NPC-CSS score in favor of arimoclomol versus placebo • Corresponds to a 101% reduction (baseline 13 26 adjusted) in disease progression

18 18 Arimoclomol has a favorable safety profile

Arimoclomol has an adverse event (AE) rate similar to • In the phase 2/3 study, a similar AE rate was observed between arimoclomol (88.2%) and placebo (81.3%) placebo and a 2.5-fold higher serious AE • Fewer SAEs occurred with arimoclomol (14.7%) than with (SAE) rate for placebo placebo (37.5%) compared with arimoclomol

19 *SAE stands for serious adverse event 5 domain NPC-CSS: 85% of NPC patients and caregivers stated in a web survey that a difference of 1 point is meaningful

Score 0 1 2 3 4 5 Domain Normal Clumsy, Ataxic, gait wider, Assisted Wheelchair bangs into things poor balance ambulation – only dependent Ambulation walk short distance indoor Normal Slight dysfunction Mild dystonia Limited skills, Unable to use Fine motor but able to handle Require little unable to use hands. Assistance skills cutlery assistance, able to pencil or eat needed for all feed without help independently activities Normal Cough while Intermittent Constant and Constant feeding Dependent Swallow eating problems with intermittent problems or use feeding by tube drink or food feeding problems of tube

Normal Mild learning Moderate learning Severe delay – Loss of cognitive delay, still in delay – need Constant function Cognition normal class special support in supervision, not Unable to school and able to learn new understand day- kindergarten skills to-day events Normal Mild slurring / Severe dysarthria Non verbal Absence of slower speech Very slow, difficult communication, communication Speech to understand Uses simple signs / pictures

20 Ref study: OR-SRV-NPC-01 sIBM ALS Neurological Gaucher Arimoclomol: a novel approach for the treatment of sIBM, directly targeting muscle degeneration

sIBM is a rare neuromuscular disease in adults Phase 2/3 Trial

• Most common idiopathic inflammatory myopathy in people over • 20-months 1:1 randomized, placebo-controlled 50 years • 152 patients (2 more randomized; over enrolled); fully enrolled • Average time to walking stick: 5 years in May 2019 • Average time to wheelchair: 10-15 years • Randomization: • Significant morbidity: propensity to fall, motor disability, • Arimoclomol 400mg (TID): n=75 swallowing failure and poor quality of life • Placebo TID: n= 75 • Death is related to falls and aspiration pneumonia

sIBM disease pathway Phase 2/ 3 Endpoints

• US & EU: up to 40,000 patients • Primary endpoint: IBM functional rating scale (IBMFRS) • No approved treatment • Secondary endpoints: • Managed in highly-specialized expert centers • 6-mins walking test with 2-mins distance captured • Affects men to women at a ratio of 3:1 • Modified time up and go • Primary treaters: Neurology and Rheumatology • Manual Muscle Testing • Isometric contraction testing of bilateral quadriceps muscle • Grip strength

22 Arimoclomol Preclinical and Phase 2 studies support MoA and potential for disease modification

83% of arimoclomol patients Preclinical Arimoclomol Phase 2 stabilized versus 25% on placebo

Double-blinded, randomized pilot trial (n=24: 16 arimoclomol; Arimoclomol effects on sIBM-like pathology*1 8 placebo) 4 months of treatment, 12-month observation period 4M (n=16 vs 8) 8M (n=14 vs 8) 12M (n=15 vs 8) 0.0 ▪ Cross-section of muscle cells from -0.5 Δ60% healthy mouse

VCP -1.0 - ▪ No inclusion bodies (aggregates) -1.5 Δ75% WT present (ubiquitin, red) -2.0 -2.5 -3.0 Δ40% ▪ Inclusion bodies (red aggregates) are -3.5 evident throughout the muscle cells -4.0 Arimoclomol 100 mg TID

Change in IBMFRS sum scoresum in Change IBMFRS -4.5 mVCP ▪ Shows degeneration of muscle tissue and Placebo decrease in muscle force -5.0

• 4 months of continuous Monthtreatment resulted in a 60% ▪ HSP70 upregulated reduction in progression with arimoclomol vs placebo

+ Ari + ▪ Inclusion bodies (aggregates) are cleared • At 8 months (4 months after treatment discontinuation) ▪ Prevents degeneration of muscle tissue 75% reduction in progression and preserves muscle force • 83% of arimoclomol treated patients were stabilized vs mVCP 25% on placebo *Mutated mice with IBM hallmarks are treated with arimoclomol from disease onset 23 (4 months) + 10 months 1.Ahmed M et al., Sci Translat Med 2016; 8:331 The Inclusion Body Myositis Functional Rating Scale (1/2)

Score Domain 0 1 2 3 4

Early eating Dietary consistency Needs tube feeding Frequent choking problems— occasional Normal Swallowing changes choking

Able to grip pen but Not all words are Slow or sloppy; all Unable to grip pen Normal Handwriting unable to write legible words are legible

Can cut most foods, Food must be cut by Somewhat slow and Needs to be fed although clumsy and someone, but can still clumsy, but no help Normal Cutting food slow; some help feed slowly needed needed

Independent but Frequently requires Fine motor requires modified Slow or clumsy in Unable assistance from Independent techniques or completing task tasks caregiver assistive devices

Requires assistance Independent but Independent but with from caregiver for requires assistive Total dependence increased effort or Normal Dressing some clothing items devices or modified decreased efficiency techniques

24 The Inclusion Body Myositis Functional Rating Scale (2/2)

Score Domain 0 1 2 3 4

Requires occasional Independent but Independent but with Completely assistance from requires use of assistive increased effort or Normal Hygiene dependent caregiver devices decreased activity

Turning in bed Unable or requires Can initiate, but not Can turn alone or adjust Somewhat slow and and adjusting total assistance turn or adjust sheets sheets, but with great clumsy but no help Normal covers alone difficulty needed

Unable to stand Requires assistance Performs with substitute Independent Requires use of arms Sit to stand from a device or motions but without use (without use of person of arms arms)

Wheelchair Dependent on Intermittent use of an Slow or mild Normal Walking dependent assistive device assistive device unsteadiness

Dependent on hand Slow with hesitation or Dependent on hand rail Climbing stairs Cannot climb stairs rail and additional increased effort; uses Normal support hand rail intermittently

25 Arimoclomol: a novel approach for the treatment of ALS, a fatal progressive neurodegenerative disease

ALS is a rare fatal progressive neurodegenerative disease Phase 3 Trial

• US & EU: up to 50,000 patients • 18-months randomized, 2:1 randomization placebo- • Two approved treatments: and edaravone controlled trial in early-stage ALS (ca.150’000 USD/ year) • 245 patients (includes 7 patients on stable edaravone); fully • Riluzole is shown to prolong survival by 2-3 months enrolled in July 2019 • Edaravone slows functional decline, but has burdensome IV • Randomization: regimen (IV infusion over 60 mins for a 14 days period; • Arimoclomol 400mg (TID): n=141 subsequent cycles are infused over 60 mins for 10 days) • Placebo TID: n= 71 • Average age of patients: 50 years

• Affects men to women at a ratio of 3:2 Phase 3 Trial Endpoints • Life expectancy 3-5 years • Leading cause of death is respiratory failure and aspiration • Primary endpoint: Combined function and survival (CAFS) pneumonia • Secondary endpoints: • Survival Learnings from PRO-ACT database applied • Function (ALSFRS-R) • ≤ 18 months since onset of weakness ALSFRS-R ≥ 35 • Pulmonary function (SVC) • Slow vital capacity (SVC) ≥ 70-80% (90% of patients have SVC ≥ 80%) *PRO-ACT database (>10’000 patients) applying machine • Mortality rate at 12 months (10%) and 18 months (35%) learning and conventional statistics to select a 26 homoegeneous patient population Arimoclomol preclinical studies support MoA and potential for disease modification

Preclinical 25% increase in lifespan of treated mice Untreated

Arimoclomol demonstrated a strong effect in two ALS mouse models even after administration Untreated mice (SOD1G93A)

following disease onset: Treated mice (SOD1G93A) treated Arimoclomol MOdel @ day 35 (pre-symptoms)

1) SOD1-model: 1

- Treated mice (SOD1G93A)

• Arimoclomol extends lifespan in SOD1-ALS survival % @ day 70 (symptoms seen)

mice by 25% SOD • Motoneuron death is prevented 2) VCP-model: • Mislocalization of TDP-43 is reverted TDP-43 pathology in mVCP mice spinal-chord is improved with • Amplifies HSP70 in the spinal cord and arimoclomol and associated with increased HSP70 ameliorates the phenotypes of the VCP mouse Healthy mice VCP mouse model model (TDP-43 in green) VCP mouse model + arimoclomol • Prevents formation of ubiquitin-rich inclusion bodies • Findings were confirmed in both patient skin cells and patient stem cell derived Model VCP motor neurons

27 *VCP: valosin containing protein Arimoclomol Phase 2 trials indicate slowing of disease progression and prolonged survival

Arimoclomol slowed disease progression in Arimoclomol slowed disease progression and improved sporadic ALS by 30% survival in SOD1-ALS

Sporadic ALS trial 0 • Arimoclomol was well tolerated • Efficacy (secondary endpoint) most pronounced in subpopulation with -2 A4V mutation (13 patients in each treatment arm) ALSFRS-R: Difference of 0.98 pts/month (A4V) and 0.50 (all)

-4 Survival: HR unadjusted: 0.59 (A4V) and 0.67 (all) in favor of

baseline R total change change total from R

- arimoclomol -6 Combined assessment of function & survival: CAFS output in favor Arimoclomol open label

ALSFRS Celecoxib placebo of arimoclomol. Treatment difference 5.92 (A4V) and 4.57 (all), -8 corresponding to +41% (A4V) and +28% (all) 0 1 2 3 4 5 6 Month FEV6: A reduction in pulmonary function decline of 33% The ALSFRS-R total; change from baseline by visit (in months) in the • Clinical Proof of Concept based on consistent and clinically meaningful open label arimoclomol study (100 mg TID; n = 69) vs the historical trends across all efficacy measures with very aggressive disease course control group is displayed

Dose ranging followed by 6-month open 12-month trial, double blinded placebo- Study label extension (not head-to-head) Study controlled, two-arm design. 1:1 randomization, design indicative of slowing disease progression design 36 patients, arimoclomol 200 mg TID

28 ALSFRS, Amyotrophic Lateral Sclerosis Functional Rating Scale Cudkowicz ME et al. Muscle Nerve 2008;38:837–44; Benatar M et al. Neurology 2018;90:e565-74 12-domain ALSFRS-R: Amyotrophic Lateral Sclerosis Functional Rating Score (1/2)

Score 0 1 2 3 4 Domain Speech combined with Detectable speech Intelligible with Loss of useful speech non-verbal disturbance Normal Speech repeating communication

Marked drooling, Slight but definitive Marked excess of Moderately excessive requires constant excess of saliva; may saliva with some saliva, may have Normal Salivation tissue have night-time drooling minimal drooling drooling

Exclusively parenteral Needs supplemental Dietary consistency Early eating problems – Normal Swallowing or enteral feeding tube feeding changes occasional choking

Able to grip pen but Not all words are Slow or sloppy; all Unable to grip pen Normal Handwriting unable to write legible words are legible

Independent and Dressing & Needs attendant for Intermittent assitance complete self-care with Total dependence Normal Hygiene self-care or substitute methods effort or decreased efficiency

29 12-domain ALSFRS-R: Amyotrophic Lateral Sclerosis Functional Rating Score (2/2)

Score 0 1 2 3 4 Domain Can cut most foods, Food must be cut by Somewhat slow and Cutting food and although clumsy and Needs to be fed someone, but can still clumsy, but no help Normal slow; some help needed handling utensils feed slowly needed

Turning in bed Can initiate, but not Can turn alone or adjust Somewhat slow and and adjusting Helpless turn or adjust sheets sheets, but with great clumsy but no help Normal covers alone difficulty needed No purposeful leg Non-ambulatory Early ambulation Walking Walks with assistance Normal movement functional movement difficulties

Mild unsteadiness or Climbing stairs Cannot do Needs assistance Slow Normal fatigue

Significant difficulty, Occurs with one or more Dyspnea considering using Occurs at rest of the following: eating, Occurs when walking None mechanical support bathing, dressing Some difficulty sleeping at Needs extra pillows in Orthopnea Unable to sleep Can only sleep sitting up night due to shortness of None order to sleep breath

Invasive mechanical Respiratory Continuous use of BiPAP Continuous use of BiPAP ventilation by intubation Intermittent use of BiPAP None during night and day during night insufficiency or tracheostomy

30 Neurological Gaucher disease: high unmet need with no approved treatment

Gaucher Disease Phase 2 Trial

• US & EU: up to 15,000 patients • 6-months placebo-controlled randomized double blind • No approved treatment for neurological symptoms trial, followed by extension phase, stratified for GD type 1 (n=23) and type 3 (n=16) • Managed in highly-specialized expert centers • 39 patients; fully enrolled in August 2019 • Gaucher Type I • Patients are treatment naïve to ERT and SRT • Most prevalent in Western countries (95% of cases) • 3 active dose arms: 100mg, 200mg, 400mg (all TID) • Up to 50% develop neurological symptoms including 5-7% with Parkinsonism symptoms • Randomization: • Gaucher Type III • Arimoclomol: n=30 • Most prevalent across rest of world (China: 95%, • Placebo: n= 10 Japan: 60%, India: 30%) Phase 2 Trial biomarkers, CSF and blood • Chronic neuronopathic GD with 100% CNS involvement • Mutations in the GBA gene cause misfolding and loss of • Chitotriosidase (traditionally used in ERT trials) activity of the glucocerebrosidase (GCase) enzyme • HSP70 • GCase activity • Glucosylsphingosine / Lyso-Gb1 (subtrate broken down by Gcase)

31 Thank you

For further information: [email protected]

32 Reference slides

33 Our story so far: building a biopharmaceutical company from pioneering scientific discovery to positive clinical outcomes

Phase II/III study Nature publication: sIBM initiated HSP70 augments lysosomal function, stabilizes lysosomal Positive NPC Acquisition of Orphazyme listed membranes, Phase II/III arimoclomol on NASDAQ Kirkegaard et al. full results

2009 2010 2011 2016 2017 2018 2019

Orphazyme founded • Science Translational Medicine Neurology publication: Randomized, publication: Heat shock protein- double-blind, placebo-controlled trial of based therapies as a platform for arimoclomol in rapidly progressive Discovery of the treating multiple lysosomal storage SOD1-ALS, Benatar et al. (Phase II function of heat shock diseases, Kirkegaard et al. study in SOD1-ALS) proteins and their • Science Translational Medicine role in stabilizing publication: Targeting protein lysosomes, by homeostasis in sporadic inclusion Phase III trial in ALS initiated Dr Thomas Kirkegaard body myositis: Preclinical and phase II clinical study of arimoclomol in Phase II trial in Gaucher Jensen and Professor sIBM, Ahmed et al. Type III initiated Marja Jäättelä • Phase II/III trial initiated NPC Positive NPC Phase II/III top line results

34 The heat shock protein response is the body’s normal defense mechanism to restore cells under stress

Heat shock response Heat shock proteins: 3 key effects Protein • Cell stress leads to cell aggregates DNA Prevent and correct dysfunction and death 1 protein misfolding: • Stress conditions induce the 2 HSPs ensure correct folding heat shock response (HSR), Protein and function of proteins a normal defense degradation mechanism to cell stress 1 • The HSR is triggered in all Prevent and degrades cells of the body 2 protein aggregates: Nucleus 3 (e.g. brain, muscle, neuron) Nascent HSPs can degrade protein under stress protein aggregates by facilitating • Triggering the HSR causes removal through degradation increased levels of heat 1 shock proteins, e.g. HSP70, HSP90, HSP40 Promote lysosomal function: Folded & functional 3 3 HSPs are biological chaperones protein promoting lysosomal function by increasing lipid and protein metabolism and removal, Lysosome thereby stabilizing lysosomal 1 membranes and preventing cell death

Misfolding

35 Our executive team has breadth of experience in discovery, clinical development and commercialization

Kim Stratton Chief Executive Officer

Anders Vadsholt Chief Financial Officer

Thomas Kirkegaard Chief Scientific Officer Jensen Orphan Disease Council Danish Cancer Society

Thomas Blaettler Chief Medical Officer

Molly Painter US President

Head of Global Product Angus Hogg Strategy

Head of Global Strategy & Julia Barr Operations

36 Working in partnership with leading institutions and patient groups

Patient Scientific and community collaboration partnerships

NPC

ALS

Financial partnerships IBM

Danish Cancer Society Gaucher

37 Arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase (GCase)

Efficacy of arimoclomol in common genotypes • Arimoclomol amplifies HSP70 leading to an increase in refolding, maturation and correct intracellular Effective in all Visualization of active GCase in GD cells localization of GCase in patient well-known mutations skin cells arimoclomol

• Arimoclomol significantly increases GCase activity

• Increase in GCase activity is confirmed in a complimentary neurological Gaucher disease stem cell model Untreated Gaucher Arimoclomol • Marked effects of arimoclomol seen patient skin cells treated Gaucher across common genotypes, patient skin cells including L444P

38 Arimoclomol has a sustained effect on slowing disease progression in NPC

CHANGE FROM BASELINE TO 24 MONTHS 5-domain NPC-CSS Change from baseline

4.50 Annual Disease Progression: FAS and excl. null mutations (n = 38) • Reduction in progression with arimoclomol during 4.25 Arimoclomol Placebo: Constant progression [*] core study was sustained during open-label extension 4.00

Placebo–arimoclomol Arimoclomol: Constant progression [*] CSS - 3.75 • Early treatment initiation had a greater benefit at 3.50

3.25 month 24 than delayed start, indicating that the 3.00 disease course was modified by arimoclomol domain NPC domain 64% - 2.75 2.50 • 64% reduction*DOUBLE vs NULL extrapolated MUTATION natural history 2.25 progression 2.00 33% 1.75 • 33% vs delayed start 1.50 1.25 • Switching to arimoclomol from placebo reduced 1.00

0.75 progression

0.50 Estimated change from baseline 5 baseline fromchange Estimated 0.25 DOUBLE FUNCTIONAL NULL MUTATIONS

0.00 0 3 6 9 12 15 18 21 24 • This analysis excludes individuals with double Time since baseline (month) functional null mutations (n = 3) in arimoclomol

Placebo-controlled phase Open-label extension treatment group who had rapid disease progression during the study Solid lines: Observed simple means +/- SE based on data obtained while patients were exposed to IMP 39 [*] Dashed lines: Model estimates from random intercept and slope model based on blinded 12 months data Early and sustained treatment with arimoclomol is superior to delayed start of treatment on miglustat alone

CHANGE FROM BASELINE OVER 24 MONTHS 5-domain NPC-CSS Change from baseline

4.50 Annual Disease Progression: FAS and on miglustat • Early and sustained arimoclomol plus miglustat 4.25 Arimoclomol Placebo: Constant progression [*] results in 72% progression reduction vs 4.00 Placebo–arimoclomol 3.75 extrapolated natural progression at 24 months

3.50 39% difference vs delayed start at 24 months CSS 3.25 • - 54% 3.00 • Delayed arimoclomol initiation still results in a 54% 2.75 72%

2.50 reduction in progression vs extrapolated domain NPC domain - 2.25 progression 2.00

1.75

1.50 39%

1.25

1.00

0.75

0.50

0.25

0.00 Estimated change from baseline 5 baseline fromchange Estimated

-0.25

-0.50

0 3 6 9 12 15 18 21 24 Time since baseline (month)

Solid lines: Observed simple means +/- SE based on data obtained while patients were exposed to IMP 40 [*] Dashed lines: Model estimates from random intercept and slope model based on blinded 12 months data