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1 HeROPA studyHRO350 in mild-to-moderate psoriasisData read-outJuly 2025 EU CT number: 2022-501850-12-00EudraCT number: 2021-003684-96ClinicalTrials.govID:NCT06125808 Arctic Bioscience AS
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Foundation for commercial discussions established, subgroups show statistical significanceKey findings•Primary endpoint PASI50 difficult to reach due high placebo rate; endpoint sensitive to disease fluctuations (as reported in October 2024)•Stricter endpoints like PGA 0/1 on per protocol population approaching significance (p = 0.07)•Relevant subgroupsshow statistical significance (p < 0.05)•Robust safety data with no serious concerns observed in the period and HRO350 is well tolerated by the patients•Combination of statistical significance in subgroups, responder analysis and robust safety data as base for planning future phase III and clinical development•Promising results going into further partner discussion this fall
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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 26 52PlaceboHRO350 Low DoseHRO350 High Dose Primary endpoint PASI50 difficult to measure in mild populationNatural disease fluctuations and limited precision on lower end of PASI scale makes it hard to show differences in PASI50 between groups for patients with mild-to-moderate psoriasisIllustration of hypothetical PASI fluctuations % of patients achieving PASI50 PASI50 (PP population) Illustrative PASI (scale 0-72) WeekFor visual illustrationonly: Fluctuations of PASI50 magnitude from baseline in a mild-to-moderate population (PASI 3-10) who naturally experience seasonal variation and episodes of spontaneous remission or worsening, versus a severe patient with PASI 30 at baseline achieving PASI50 (biologics trial). PASI50: The proportion of patients with ≥50% reduction in Psoriasis Area and Severity Index (PASI, scale from 0-72) from baseline. PP: Per Protocol Population for PASI. Week 52 n = 273. Data as observed. ITT: Intention to treat. N = 521, data not shown.p= 0.472 high dose, p = 0.626 low dose (week 52)1) Papp KA et al., Dermatol Ther (Heidelb) (2021) 11:1079–1083. https://doi.org/10.1007/s13555-021-00572-2 p = 0.769 high dose vs PBO (week 52)p = 0.679 low dose vs PBO (week 52) 0 5 10 15 20 25 30 35 40 45 50 0 26 52 Mild-to-moderate patients p = 0.635 high dose vs PBO (week 26)p = 0.113 low dose vs PBO (week 26) SeverepatientHeROPA Comments •PASI50 compared between HRO350 and placebo at 6 months was the primary endpoint, which was not met •Efficacy of HRO350 observed as assumed in protocol for patients who completed 1 year of treatment•Placebo response-rate was much higher than predicted•PASI scale has less precision in mild disease1
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0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 Low DoseHRO350 High Dose Stricter endpoint differentiates better: PGA 0/1 (clear or almost clear) Key secondary endpoint: Physician's Global Assessment (PGA 0/1) is easier to measure and more difficult to achieve Patients achieving PGA 0/1 (PP population) •Nearly half of patients treated with HRO350 achieved clear-or-almost clear skin after 52 weeks•PGA 0/1 is a much harder endpoint to reach than PASI50•47% of patients in the high dose arm achieved a PGA 0/1 at week 52, versus 34% in the placebo group (p = 0.073)•In the previous Haukeland study1 40% of patients achieved PGA 0/1 after 65 weeks•All patients had PGA scores ≥ 2 and ≤ 4 at inclusion StaticPGA (sPGA) measuresphysician’simpressionat a single time point. Staticform is standard due to reliability1. Tveit KS et al. Long TermEfficacy and Safety of Herring Roe Oil in the Treatment of Psoriasis, a 39-week Open-label Extension Study.International Journal of Clinical and Experimental Medical Sciences.Vol. 7, No. 1, 2021, pp. 13-20. doi: 10.11648/j.ijcems.20210701.13. 2) 3) Stein Gold L, et al.Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlledtrial.J Am AcadDermatol. 2022 Jan;86(1):77-85. doi: 10.1016/j.jaad.2021.07.040. PMID: 34343599.. % of patients achieving PGA 0/1 PP: Per Protocol population for sPGAfor patients who completed 52 weeks: n = 272. Data as observed. ITT: Intention to Treat population for sPGA: N = 521. (Non-Responder Imputation analysis not shown. p = 0.490 for high dose vs placebo and p = 0.608 for low dose vs placebo) Week p = 0.073high dose vs PBO (week 52)p = 0.144 low dose vs PBO (week 52) Comments
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0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 High Dose Higher placebo rate in patients with milder disease at baselineSubanalysisidentified differentiators on placebo response: Baseline severityAll Patients achieving PGA 0/1 (PP) •Post-hoc analysis: Placebo response is higher in patients with PASI < 6 at baseline •Patients with PASI ≥ 6and < 6 respond similarly in the high dose arm StaticPGA measuresphysician’simpressionat a single time point. Staticform is standard due to reliability. PASI < 6 at baseline (PP)PASI ≥6 at baseline(PP) Week p=0,092 p = 0.073 high dose vs PBO (week 52) 0%10%20%30%40%50%60%70%80%90%100% 0 2652PlaceboHRO350 High Dose p = 0.092 high dose vs PBO (week 52) 0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 High Dose p = 0.559 high dose vs PBO (week 52) Comments % of patients achieving PGA 0/1 Post-hoc analysis on the Per Protocol (PP) Population for sPGA. Week 52 n=272. Data as observed. ITT: Intention to treat. N = 521 all time points. (Non-Responder Imputation analysis not shown. p = 0.490, p = 0.995, and p = 0.391 for high dose vs placebo) (n = 39) (n = 44)(n = 97) (n = 85) (n = 58) (n = 41)
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0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 High Dose0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 High Dose0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 High Dose Lower placebo rate in patients ≥ 50 yearsSubanalysisidentified statistically significant subgroup: Impact of ageAll Patients achieving PGA 0/1 (PP) •Post-hoc analysis: Lower placebo rates ≥ median age( ≥ 50 years)•Younger age with shorter duration of psoriatic disease may increase chance of spontaneous improvement in the placebo group•Patients ofall ages respond similarly in the high dose arm StaticPGA measuresphysician’simpressionat a single time point. Staticform is standard due to reliability Week Post-hoc analysis on the Per Protocol (PP) Population for sPGA. Week 52 n = 272. Data as observed. ITT: Intention to treat. N = 521 all time points. (Non-Responder Imputation analysis not shown. p = 0.490, p = 0.254, and p = 0.946 for high dose vs placebo) p = 0.073 high dose vs PBO (week 52) Comments % of patients achieving PGA 0/1 Patients ≥ 50 years (PP)p = 0.043 high dose vs PBO (week 52) Patients < 50 years (PP)p = 0.548high dose vs PBO (week 52) *p < 0.05 (n = 48) (n = 42)(n = 97) (n = 85) (n = 49) (n = 43)
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0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 High Dose Higher response rates in active arm for patients with weight ≤ 98 kgsSubanalysisidentified statistically significant subgroup: Impact of weightAll Patients achieving PGA 0/1 (PP) •Post-hoc analysis showed that more patients in lower three weight quartiles (patients weighing ≤ 98 kgs) in PP achieved a PGA 0/1 at week 52 than patients in the highest weight quartile StaticPGA measuresphysician’simpressionat a single time point. Staticform is standard due to reliability Week Post-hoc analysis on the Per Protocol (PP) Population for sPGA. Week 52 n = 272. Data as observed. ITT: Intention to treat. N = 521 all time points. (Non-Responder Imputation analysis not shown. p = 0.490, p = 0.469, and p = 0.868 for high dose vs placebo). Missing weight: n = 2 PBO p = 0.073 high dose vs PBO (week 52) Comments % of patients achieving PGA 0/1 0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 High Dose Weight ≤ 98 kg (PP) 0%10%20%30%40%50%60%70%80%90%100% 0 26 52PlaceboHRO350 High Dose p = 0.041 high dose vs PBO (week 52) * Weight > 98 kg (PP)p = 0.708high dose vs PBO (week 52) p < 0.05 (n = 74) (n = 67)(n = 97) (n = 85) (n = 21) (n = 18)
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Robust safety on HRO350 No Serious Safety ConcernsNo drug-related Serious Adverse Events (SAEs) or Suspected Unexpected Serious Adverse Reactions (SUSARs) were reportedIndependent Oversight Confirmed SafetyPeriodic reviews by the independent Data Monitoring Committee (DMC) raised no safety concerns throughout the trialWell Tolerated Over 1 YearHRO350 demonstrates a favorable safety profile throughout 12 months of treatment and 2 months post-treatment follow-up Few drug-related adverse events (AEs) and low drop-outs due to drug-related AEsAdverse events observed were consistent with expectations and those seen in the Haukeland studyRegulatory-Ready DocumentationFull safety data analysis, including frequency tables and SAE narratives will be detailed in the Clinical Study Report HRO350 safety from HeROPApatients (N = 521) treated for up to 1 year Well tolerated with no serious safety concerns
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Plan going forward •Nutra business is growing strongly (~30 % annually)•We strongly believe there is a major market potential for HRO350 in mild-to-moderate psoriasis•Arctic Bioscience will seek partnerships for further development of HRO350 with a potential Phase III clinical program
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10 Q&A
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11 Appendix
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12 HRO350 in mild-to-moderate psoriasisMarket and value proposition
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*Split between mild and moderate patients varies in the literature.Sources: HRO350 Commercial Opportunity Assessment in Psoriasis, IQVIA; WHO Global Report on Psoriasis; Rendon. Int J Mol Sci.2019 Mar; 20(6): 1475; UpToDate;American Academy of Dermatology Association; Papp. Dermatol Ther. 11:1053; 2021; National Psoriasis Foundation; Evaluate Pharma 2022 Psoriasis Market Size, November 2022 Analysis. Split of Disease Severity 4E Mild-to-Moderate In the U.S., 50% of patients (~5M)In the EU5, 66% of patients (~7.8M) PASI < 3/5*3/5* < PASI < 10 In the U.S., 30% of patients (~3M)In the EU5, 25% of patients (~2.9M) Moderate-to-Severe and Severe PASI > 10 In the U.S., 20% of patients (~2M)In the EU5, 11% of patients (~1.3M) ~18.7M mild-to-moderate patients in the U.S. and EU5HRO350 Strategic Positioning: mild-to-moderate psoriasis •~22.5M total psoriasis patients across severity types (~10.7 U.S. and ~11.8 EU5)•~80% of U.S. patients and ~90% of EU5 patients have mild-to-moderate psoriasis•HRO350 is targeting a total addressable market of ~18.7M mild-to-moderate psoriasis patients
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•Drug development program for children <18 years of age with psoriasis•Component of the regulatory drug development journey for HRO350•Prerequisite for filing for marketing authorization (MA) for new medicines in Europe Limited approved products in standards of careHigh unmet medical needPaediatricInvestigation Plan (PIP) agreed with the PaedatricCommittee* of the EMA •A futurepaediatricindication would increase patient population who could have benefit from HRO350•1% of children under age 18 suffer from psoriasis•Plan for expanded indication for HRO350•Limited treatment options –potential first line treatment for mild-to-moderate psoriasis in children•Unmet need for oral treatments –only apremilast currently in clinical trials for mild-to-moderate pediatric psoriasis (> 6 yrs) in the US *The PaediatricCommittee of the EMA provides opinions on the quality, safety and efficacy of a medicine for use in the paediatricpopulationReferences:Augustin M, GlaeskeG, Radtke MA, Christophers E, Reich K, Schäfer I. Epidemiology and comorbidity of psoriasis in children. Br J Dermatol. 2010 Mar;162(3):633-6. doi: 10.1111/j.1365-2133.2009.09593.x. Epub2009 Nov 18. PMID: 19922529; HaulrigMB, ZachariaeC, SkovL. Off-Label Treatments for Pediatric Psoriasis: Lessons for the Clinic. Psoriasis (Auckl). 2021 Feb 11;11:1-20. doi: 10.2147/PTT.S268462. PMID: 33604269; PMCID: PMC7886293.; MenterA, CordoroKM, Davis DMR, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the managementand treatment of psoriasis in pediatric patients [published correction appears in J Am AcadDermatol. 2020 Mar;82(3):574].J Am AcadDermatol. 2020;82(1):161-201. Potential first-line treatment for children with mild-to-moderate psoriasisPaediatric indication for HRO350: upside potential
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PASI: Psoriasis Area and Severity Index (0-72 pointscale where >10 is moderate-to-severe and severe disease)Source: HRO350 Commercial Opportunity Assessment in Psoriasis, IQVIA report*Oral (e.g.fumarates, methotrexate, apremilast)** Injectables (e-g-. adalimumab, ustekinumab, ixkizumab) Mild-to-Moderate(PASI<10)Moderate-to-Severe(PASI>10) TopicalPrimarily corticosteroidsanthralin, calcipotriene Light therapyPUVA Systemic*(e.g., oral fumarates, methotrexate, apremilast, JAK and TYK inhibitors) Biologic**(e.g., injectables adalimumab, ustekinumab, ixkizumab,) AdministrationActive substancePsoriasis indicationSeverity Oral (soft capsules)First-in-class active pharmaceuticalingredient (API)Mild-to-moderate diseaseFew treatment options for non-severe disease HRO350 could meet an unmet medical need for patients with non-severe psoriasis HRO350 target population80-90% ofpsoriasis patients Market opportunityin mild-to-moderate diseaseProperties ofdrugcandidateHRO350
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16 HeROPA studyHRO350 in mild-to-moderate psoriasisStudy design
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Large phase IIb study investigated efficacy, safety, and dose of HRO350 versus placeboHeROPA Phase IIb clinical trial design•Included 521 patients started late January 2023 in the UK and March 2023 in Germany, Poland, Finland and Norway•Protocol designed based on Scientific Advice from the EMA PASI: Psoriasis Area and Severity Index (0–72-point scale where < 10 is mild-moderate disease); RCT: Randomized Controlled Trial. U CT number: 2022-501850-12-00EudraCT number: 2021-003684-96b.d.= twice daily; iii = three capsules; DDD = defined daily dose Period A : RCT (week 0-26) Period B : RCT(week 26-52) Follow-up (week 52-60) Primary Endpoint at week 26PASI 50 Secondary Endpoints at week 52Including Change in PASI
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HRO350is a uniquelipid matrix with biologically active phospholipids Proprietary lipid extract of phospholipid esters fromherring roe(Clupea harengus)Manufactured according to GMPCellular data on API and immunomodulation1-3 Active substance (API): PEHeRo(Phospholipid Esters from Herring Roe) IRIS Substance ID: 300000046327EV MedicinalProduct Code: PRD9919073 Core structure of phospholipid esters from herring roe FATTY ACID GLYCEROL FATTY ACID ALCOHOL PO4 AB D C E ABCDE Example phospholipid: PC(22:6n3/16:0) API: Active Product Ingredient; GMP: Good Manufacturing PracticeReferences: 1) Forskningsradet(Research Council of Norway), Properties of phospholipids d Herring Roe in Psoriasis, available online2) Ringheim-Bakka, TA et al. Herring roe PLs promote SPM biosynthesis in macrophages and a keratinocyte/fibroblast co-culture as model of psoriasis, PREPRINT, bioRxiv2025.02.20.639253; doi: https://doi.org/10.1101/2025.02.20.639253. 3) Mildenberger, J et al. Herring roe oil exerts anti-psoriatic and immunomodulatory effects on the IL-17/23 signaling axis in macrophages, T-cells and a keratinocyte and fibroblast co-culture, PREPRINT, bioRxiv2025.04.22.650092; doi: https://doi.org/10.1101/2025.04.22.650092. HRO350 is a first in class asset with phospholipid esters as API
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HRO350Mode of action & resolution of inflammation
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Specialized pro-resolving mediators (SPMs) are a type of bioactive lipids that actively terminate inflammation and drive the restauration of tissue homeostasis 1 Lipidmediators are elevated in lesional psoriatic skin3. Most existing drugs are designed to reduce inflammation by inhibiting pro-inflammatory cytokines Data on SPMs supporting an anti-inflammatory action of HRO350, and PEHeRospecifically •upregulating the production of SPMs which promote a shift towards a protective and possibly reparative phenotype of monocyte-derived macrophages HRO350 API (PEHeRo) promotes SPM biosynthesis in immune cells with implications for the treatment of psoriasisResolve -not block -inflammation: a therapeutic frontier Fullerton, J., Gilroy, D. Resolution of inflammation: a new therapeutic frontier.Nat Rev Drug Discov15, 551–567 (2016). https://doi.org/10.1038/nrd.2016.39Park J, Langmead CJ, RiddyDM. New Advances in Targeting the Resolution of Inflammation: Implications for Specialized Pro-Resolving Mediator GPCR Drug Discovery ACS Pharmacol. Transl. Sci.2020, 3, 1, 88–106;Serhan CN, Chiang N, Dalli J. The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution. Seminars in Immunology. 2015 May;27(3):200-215. DOI: 10.1016/j.smim.2015.03.004. PMID: 25857211; PMCID: PMC4515371.Ringheim-Bakka T,MildenbergerJ, DalliJ, SalianiA, PetrucelliF, BusyginaM, MancinelliD, GammelsæterR.Phospholipid Esters from Herring Roe promotes SPM biosynthesis in human monocyte-derived macrophages with implications for the treatment of psoriasis.Poster (37) at the 9th European Workshop on Lipid Mediators, June 26-28th, 2024. 1 2 3 4
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21 HRO350Clinical development plan
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HRO350 drug development program in psoriasisUpdated plan MAA: Marketing Authorization Application; IMP: Investigational Medicinal Product. MoA: Mode of Action; IMPD: Investigational Medicinal Product Dossier; CTA: Clinical Trial Application. Scientific Advice with EMA. PIP: Paediatric Investigation Plan agreed with with the EMA Pediatric Committee*in Q1 2022. 20232022202420252027 Cellular studies MoA 2026202820192020202120182017 Pharmacokinetic study The HePhase III clinical programPilot clinical trialThe HeROPA Phase IIb clinical trial Clinical GMP development of IMP HRO350Formulation for children Product Paediatric clinical development PaediatricPre-clinical Scientific Advice Regulatory PIPCTA MAA in adultsPre-IND USA 2029
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23 HeROPA investigators and clinics:Norway:Haukeland University HospitalÅlesundhospitalStavanger University HospitalNordlandssykehusetUnited Kingdom:Salford Royal hospitalKiltearnMedical CentreNewquay Health CentreWaterloo Medical CentreHeart of Bath SurgeryUniversity Hospitals DorsetSherbourne Med CentreUniversity Hospital of DurhamThe practice of healthTrowbridge Health CentreSt Clare Medical centreKingsmill HospitalLakeside Medical ResearchSuffolk Primary Care -Haven HealthBreckland Alliance -Grove SurgeryConcord Medical CentreRoyal Primary Care AshgateHoniton SurgeryHathaway Medical CentreRowden SurgeryWest Walk SurgeryClarence Medical CentreCarn to Coast Health CentresFinland:CRST HelsinkyOyCRST Turku Oy Germany:FachklinikBad BentheimDerma-Study-Center-FN GmbHUniversitätsklinikumMünster (UKM)HautarztpraxisDr. med. Matthias HoffmannUniversitätsklinikumHeidelbergTU DresdenHaut-und LaserzentrumHunsrückStudienzentrumDr. Leitz Tri-DermPro DermaUniversity Clinic UKSH KielIsa Research UniversitätsklinikumEssenHautmedizinBad Soden StudienzentrumLMU KlinikumStudienzentruman der Hase GbRRosenparkResearch GmbHDermatologieQuistZentrum für Dermatologieund Ästhetik, FriedrichsdorfUniversitätsklinikumErlangenMensingdermAresearch GmbH, HamburgPoland:MICS Centrum MedyczneToruńKlinicznychCentrum MedyczneAll-MedKO-MED Centra KliniczneSp. z o.oPulawyOsrodekWsparciaBadan KlinicznychKOMED at NarodowyInstytutGeriatriiDermoklinikaCentrum MedyczneRENEW ClinicKlinikaAmbroziakKlinikaOsipowiczI Turkowski sp. zo.o.Dr. SękowskaKlinikaLeczeniaBóluInstytutZdrowiaDr. Boczarska-Jedynak Our CRO: Smerud Medical Research International Thank you: Norwegian Research councilInnovation NorwaySparebank1 SMNEksfinOur gratitude to the patients who participated in the HeROPA study THANK YOU
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Matters discussed in this Presentation may constitute or include forward-looking statements. Forward-looking statements are statements that are not historical facts and may include, without limitation, any statements preceded by, followed by or including words such as “aims”, “anticipates”, “believes”, “can have”, “continues”, “could”, “estimates”, “expects”, “intends”, “likely”, “may”, “plans”, “forecasts”, “projects”, “should”, “target” “will”, “would” and words or expressions of similar meaning or the negative thereof. These forward-looking statements reflect the Company's beliefs, intentions and current expectations concerning, among other things, the Company's results of operations, financial condition, liquidity, prospects, growth and strategies. Forward-looking statements involve known and unknown risks and uncertainties because they relate to events and depend on circumstances that may or may not occur in the future. The forward-looking statements in this Presentation are based upon various assumptions, many of which are based, in turn, upon further assumptions that may not be accurate or technically correct, and their methodology may be forward-looking and speculative. An investment in the Company's shares should be considered as a high-risk investment. Several factors could cause the actual results, performance or achievements of the Company to be materially different from any future results, performance or achievement that may be expressed or implied by statements and information in this Presentation. A multitude of factors can cause actual results to differ significantly from any anticipated development expressed or implied in this Presentation, including among others, economic and market conditions in the geographic areas and industries that are or will be major markets for Company's businesses, changes in governmental regulations, interest rates, fluctuations in currency exchange rates and such other factors. The information obtained from third parties has been accurately reproduced and, as far as the Company is aware and able to ascertain from the information published by that third party, no facts have been omitted that would render the reproduced information to be inaccurate or misleading. The contents of this Presentation are not to be construed as financial, legal, business, investment, tax or other professional advice. By receiving this Presentation, the Recipient acknowledges that it will be solely responsible for its own assessment of the Company, the market and the market position of the Company and that it will conduct its own analysis and is solely responsible for forming its own opinion of the potential future performance of the Company’s business. In making an investment decision, the Recipient must rely on its own examination of the Company, including the merits and risk involved. This Presentation is not an advertisement for the purposes of applicable measures implementing the EU Prospectus Regulation. This Presentation is not a prospectus and does not contain the same level of information as a prospectus. Disclaimer Note: For sources, references and additional context recipients of this presentation are referred to the Company Presentations found on Arctic Bioscience website, https://arctic-bioscience.com/investors/reports-presentations/
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25 ContactArctic Bioscience ASBusiness address: Industrivegen426155 ØrstaNorwaywww.arctic-bioscience.com CEO: Christer Valderhaugchrister@arctic-bioscience.comPhone: +47 92084601 Medical Director: Runhild Gammelsæterrunhild@arctic-bioscience.comPhone: +47 95933436