VICORE PHARMA AB. A Rare Disease Company with a Focus on Patients with Fibrotic Lung Disease

VICORE PHARMA AB A Rare Disease Company with a Focus on Patients with Fibrotic Lung Disease 1

FORWARD LOOKING STATEMENT This presentation may contain certain forward-looking statements and forecasts based on uncertainty, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on Vicore Pharma s business, financial condition and results of operations. The terms anticipates, assumes, believes, can, could, estimates, expects, forecasts, intends, may, might, plans, should, projects, will, would or, in each case, their negative, or other variations or comparable terminology are used to identify forward-looking statement. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied in a forward-looking statement or affect the extent to which a particular projection is realized. Factors that could cause these differences include, but are not limited to, implementation of Vicore Pharma s strategy and its ability to further grow, risks associated with the development and/or approval of Vicore Pharma s products candidates, ongoing clinical trials and expected trial results, the ability to commercialize C21, technology changes and new products in Vicore Pharma s potential market and industry, the ability to develop new products and enhance existing products, the impact of competition, changes in general economy and industry conditions and legislative, regulatory and political factors. No assurance can be given that such expectations will prove to have been correct. Vicore Pharma disclaims any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. 2

VICORE AT A GLANCE FOCUS Patients with fibrotic lung disease GUIDING PRINCIPLE Unmet medical needs every day matters PIPELINE Two clinical stage differentiated and complementary assets INDICATIONS 1) IPF 2) pulmonary sarcoidosis, systemic sclerosis and other fibrotic lung diseases evaluated DIFFERENTIATION Addressing fibrosis and vasculopathy; improving cough and QoL PEOPLE Team of experienced drug developers SHARE Listed on Nasdaq First North 3

EXPERIENCED TEAM CARL-JOHAN DALSGAARD, CEO MD, PhD, Karolinska Institute with post-doc experience from Harvard Medical School Former Head of Therapy Area Pain Control, AstraZeneca R&D 10 years of experience from senior management, AstraZeneca 18 years of experience as Venture Partner at HealthCap HANS JEPPSSON, CFO PhD, Finance Finance professional with cross-disciplinary background in finance and medicine Former equity research analyst at Danske Bank and post-doc research at UC Berkeley Professor in Finance at Gothenburg School of Economics and Law ROHIT BATTA, CMO MBBS, King s College London, MFPM Medical doctor with extensive industry experience in Rare Diseases Joins us Nov 18 from GSK, where he led the global medical and clinical development of the world s first paediatric gene therapy JOHAN RAUD, CSO MD, PhD, Karolinska Institutet Former Director Inflammation research AstraZeneca Investment Manager KIF 25 years of experience in drug development KICKI JOHANSSON, HEAD OF DRUG DEVELOPMENT MSc Pharm, PhD Former Senior Project Leader/VP AstraZeneca Accountable for the development of over 40 new compounds Approximately 30 years experience of drug development OLA CAMBER, CMC MSc, PhD, Uppsala University Former Director Pharmaceutics & Biopharmaceuticals, Pharmacia Former Director Astra Zeneca, Pre-formulation & Biopharmaceuticals More than 30 years of experience in drug development GÖRAN TORNLING, SENIOR MEDICAL ADVISOR MD, PhD, Karolinska Institutet Medical doctor and Pulmonologist with more than 20 years of clinical experience Former Director Clinical Strategy, AstraZeneca and responsible for IPF study designs JOHANNA GRÄNS, REGULATORY AFFAIRS MANAGER MSc, PhD, University of Gothenburg Extensive experience in preclinical R&D Research experience in drug metabolism 4

5 FIBROTIC LUNG DISEASE

FIBROTIC LUNG DISEASE CLINICAL PICTURE In the fibrotic lung, vasculopathy and tissue scarring dominate the pathology This leads to dyspnoea and cough, as the main symptoms As disease progresses, patients develop increased pulmonary artery pressure, which aggravates hypoxia Pulmonary hypertension (PH) is the leading cause of death in fibrotic lung disease 6

PATHOPHYSIOLOGY FIBROTIC LUNG DISEASE LUNG TISSUE INTERSTITIAL FIBROSIS FIBROTIC MEDIATORS STRETCH ACTIVATION COUGH IMPAIRED QoL LUNG RESISTANCE VESSEL FIBROTIC MEDIATORS VASCULOPATHY IMPAIRED GAS EXCHANGE HYPOXIA VASOCONSTRICTION DYSPNOEA PH/HEART FAILURE DEATH Vasculopathy and interstitial fibrosis are the drivers of disease 7

FIBROTIC LUNG DISEASE - INDICATIONS Idiopathic pulmonary fibrosis Systemic sclerosis Sarcoidosis Pneumoconioses CH pneumonitis Other 8

FIBROTIC LUNG DISEASE Someone dies of pulmonary fibrosis every 13 minutes Let the world know 9

FIBROTIC LUNG DISEASE THE PATIENT A 74-year-old man with worsening, chronic, non-productive cough and dyspnoea on exertion is diagnosed with IPF After several years of stable disease, the patient began to decline rapidly Attempts at slowing disease progression, including switching from pirfenidone to nintedanib, providing home oxygen, and beginning tadalafil therapy for PH were unsuccessful A variety of medical therapies were unable to control the cough Because of his age and multiple comorbidities, the patient did not qualify for lung transplantation, despite his end-stage disease To be continued. 10

IDIOPATHIC PULMONARY FIBROSIS (IPF) IPF is a severe and devastating disease, often with a 3-5 year survival after diagnosis Prevalence is about 250,000 patients in the US and EU Symptoms include dyspnoea and a severe dry cough There is a strong correlation between cough and progression 30-80% also have PH 11

FVC (ml) TWO DRUGS AVAILABLE FOR IPF 0 Efficacy of pirfenidone and nintedanib Uptake of pirfenidone since 2011 Pirfenidone Pirfenidone Nintedanib Nintedanib in a Swedish cohort 6 months* 12 months* 6 months** 12 months** n=624 n=623 n=624 n=623 n=475 n=664 n=408 n=580 On drug -100-200 On drug <12 months -300-400 -500 PLACEBO ACTIVE *Noble 2016 **Richeldi 2016 SIDE EFFECT PROFILE OF PIRFENIDONE AND NINTEDANIB Pirfenidone GI, skin, liver Nintedanib GI, liver No drug Ferrara ERS 2018 Approved drugs have had a low uptake due to suboptimal efficacy/side effect profile 12

PULMONARY SARCOIDOSIS (PS) Corticosteroid-resistant pulmonary sarcoidosis is a devastating disease with high morbidity and mortality The prevalence of severe pulmonary disease is about 250,000 patients in the US and EU The disease is auto-inflammatory, characterized by granuloma formation As the disease progresses, the patient develops PH and lung transplantation is the only cure 13

SYSTEMIC SCLEROSIS WITH PULMONARY FIBROSIS Systemic sclerosis (SSc) is a chronic, progressive autoimmune disease leading to vasomotor disturbances, fibrosis, and subsequent atrophy of small arteries of the skin and internal organs Interstitial lung disease (ILD) develops in 50% of patients after 5 years and PH in 25%, and is the leading cause of death SSc-ILD is considered to be a result of both alveolar and vascular damage 14

MEDICAL NEEDS IN FIBROTIC LUNG DISEASE Patients with pulmonary fibrosis want to: Feel well Reduce dyspnoea without side effects Stop coughing Reduce cough Live longer Reduce or prevent fibrosis, vasculopathy, and PH None of today s medicines meet the needs of the patients 15

16 VP01 (C21)

VP01 (C21) CLASS First in class small molecule angiotensin II type 2 receptor (AT2r) agonist with ODD for IPF (EU, US) SELECTIVITY 10,000 x higher affinity for AT2r compared with AT1r PRESENTATION Oral with 20-30% bioavailability PRECLINICAL Excellent preclinical fibrosis data SAFETY Well tolerated in toxicology studies; first sign is natriuresis CLINICAL Phase I safety study completed, up to 100mg daily safe and well tolerated STATUS Initiation of a dose escalation study followed by a phase IIa study 17

AT2r A NEW TYPE OF PEPTIDE RECEPTOR Tate 2017 The AT2r is upregulated and active during fetal development and then only in processes of scarring and regeneration 18

AT2r IN FIBROTIC LUNG DISEASE TISSUE INJURY SUBACUTE FIBROPROLIFERATIVE PHASE PROGRESSIVE OBLITERATION OF INTERSTITIAL, ALVEOLAR, AND VASCULAR COMPARTMENTS AT1r AT2r REPAIR FIBROSIS Induces TGF-b and procollagen ANGII C21 ANTIFIBROTIC Reduces TGF-b and procollagen 19

RVSP (mmhg) RVDP (mmhg) C21 REDUCES PH IN A FIBROTIC LUNG DISEASE MODEL The monocrotaline model is a chemically induced lung fibrosis model regarded as the standard model for pulmonary hypertension Right Ventricular systolic pressure Right Ventricular diastolic pressure 100 $ 10 80 # 8 # 60 6 40 4 20 2 0 Control MCT MCT+C21 MCT+C21+PD 0 Control MCT MCT+C21 MCT+C21+PD Bruce 2015 Effect on pulmonary hypertension is important for outcome and has not been shown for existing therapies 20

C21 REDUCES FIBROSIS IN LUNGS OF MICE TREATED WITH BLEOMYCIN Reduction of fibrosis score (D compared with placebo) when drugs are given as prevention 0% Esbriet Pirfenidone Roche 50mg/kg Ofev Nintedanib B-I 60mg/kg Pamrevlumab anti-ctgf FibroGen 30mg/kg C21 0.03mg/kg -20% -40% -60% -23% -38% -41% -80% -100% -65% Wollin 2014 Heckmann 2016 Rathinasabapathy 2018 C21 produces the largest reduction in fibrosis score in the bleomycin model when given as prevention 21

C21 REDUCES FIBROSIS IN LUNGS OF MICE TREATED WITH BLEOMYCIN 0% -20% Esbriet Pirfenidone Roche 50mg/kg -1% Reduction of fibrosis score (D compared with placebo) when drugs are given as treatment Ofev Nintedanib B-I 60mg/kg -10% Pamrevlumab anti-ctgf FibroGen 30mg/kg C21 C21 0.03mg/kg -40% -60% -38% -45% -80% -100% Wollin 2014 Heckmann 2016 Rathinasabapathy 2018 C21 is comparable to the best drugs in reducing fibrosis score in the bleomycin model when given as treatment 22

C21 INHIBITS COLLAGEN DEPOSITION IN LUNGS OF MICE TREATED WITH BLEOMYCIN Reduction in collagen increase (D hydroxyproline) Reduction of increased CTGF expression Pirfenidone Roche Pamrevlumab anti-ctgf, FibroGen C21 C21 0% 10mg /kg 30mg /kg 100mg /kg 3mg /kg 10mg /kg 30mg /kg 0.03mg/kg 0% 0.03mg/kg -20% -13% -20% -40% -27% -27% -38% -40% -60% -80% -58% -64% -60% -80% -100% -100% -100% -91% Oku 2008 Wang 2011 Rathinasabapathy 2018 C21 completely inhibits CTGF expression and collagen deposition induced by bleomycin 23

AT2r IS UPREGULATED IN HUMAN FIBROTIC LUNG 10% Total AT2r quantification Control Septal areas Vessels 8% 6% 4% IPF 2% 0% Control IPF SSc AT2r is increased in IPF and SSc SSc Vascular AT2r negatively correlates with DLCO and mortality Parra 2014 Parra 2014 24

AT2r STIMULATION DILATES HUMAN RESISTANCE VESSELS Coronary microvessels Fat tissue microvessels in T2DM Effect of AT1r- and AT2r-blockade on ANG II contraction Effect of AT1r- and AT2r-blockade on ANG II relaxation of precontracted vessels p<0.05 AT1r antagonist AT2r antagonist Batenburg 2004 Savoia 2007 Batenburg 2004 Savoia 2007 AT2r induces endothelial-dependent, nitric oxide mediated, vasodilatation in human resistance vessels 25

C21 MODIFIES IPF BIOMARKERS IN VITRO Collagen biomarkers predict severity, progression, and mortality in IPF; C21 modulates collagen biomarker expression in vitro Effect on human primary lung fibroblasts + alveolar epithelial cells in co-culture stimulated with TGFb and TNFa Vicore, data on file 0,5 C21 reduces collagen III expression 0,5 C21 increases MMP1 expression 0,4 0,4 0,3 0,3 0,2 0,2 0,1 0,1 0 C21 10mM C21 3.3mM C21 1.1mM Pirfenidone 1700mM Nintedanib 1.1mM 0 C21 10mM C21 3.3mM C21 1.1mM Pirfenidone 1700mM Nintedanib 1.1mM C21 dose-dependently reduces markers of collagen formation and increases markers of collagen degradation 26

C21 - PHASE I DOSE ESCALATION DESIGN Blinded 8 subjects per group; 6 active and 2 placebo DOSES 100mg BID; 200mg BID; 200mg TID (multiple ascending dose) DURATION 8 days FOOD INTERACTION One group (single ascending dose) BIOMARKERS Exploratory biomarkers PLACE AND TIME Parexel, Berlin (or UK), start dosing first cohort January 2019 27

C21 - PHASE II IPF DRAFT SYNOPSIS DESIGN Double-blind controlled 3 month study POPULATION Naïve INCLUSION Select progressing patients based on biomarker or high-resolution computed tomography (HRCT) NUMBERS 50 patients with a 1:1 distribution (active: placebo) only high recruitment sites ENDPOINT Safety as primary and forced vital capacity (FVC)/HRCT/biomarkers as secondary DOSE To be decided after the phase I dose escalation SITES Principal investigator: Joanna Porter, London sites in UK and Eastern Europe 28

C21 IN FIBROTIC LUNG DISEASE LUNG TISSUE INTERSTITIAL FIBROSIS FIBROTIC MEDIATORS STRETCH ACTIVATION COUGH IMPROVED QoL LUNG RESISTANCE VESSEL FIBROTIC MEDIATORS VASCULOPATHY IMPAIRED GAS EXCHANGE HYPOXIA VASOCONSTRICTION DYSPNOEA HEART FAILURE INCREASED SURVIVAL C21 reduces Fibrosis and Vasculopathy 29

30 VP02 (IMID)

IMiD (IMMUNOMODULATORY DRUG) CLASS Includes pomalidomide, lenalidomide, and thalidomide SELECTIVITY Broad anti-inflammatory and antifibrotic action PRESENTATION Local pulmonary delivery PRECLINICAL Excellent preclinical fibrosis data and a strong TNF inhibitor SAFETY Clinical systemic side effects include myelopathy, sensory neuropathy, gastrointestinal (GI) effects, and sedation CLINICAL Systemic IMiDs show dramatic effects on IPF and IPF cough, QoL, and steroid-resistant sarcoidosis 31

IMiD MOLECULAR MODE OF ACTION CD147 Cereblon (CRBN) is the substrate receptor of the E3 ubiquitin ligase complex Activation promotes various biological functions, including angiogenesis, proliferation, invasion, and immune response MCT-1 Rabex-5 CRBN CRBN Golgi IMiD O N O O N H O IMiDs outcompete cereblon to reduce its biological function, including maturation of CD147, an auto-inflammatory antigen Endoplasmic reticulum CRBN Nucleus Millrine 2017 32

THALIDOMIDE REDUCES FIBROSIS IN THE LUNGS OF MICE TREATED WITH BLEOMYCIN 0% -20% Esbriet Esbriet Pirfenidone Roche 50mg/kg -1% Reduction of fibrosis score (D compared with placebo) when drugs are given as treatment -10% Ofev Pamrevlumab C21 Ofev Pamrevlumab C21 Thalidomide Nintedanib B-I 60mg/kg anti-ctgf FibroGen 30mg/kg 0.03mg/kg 4mg/kg -40% -60% -38% -45% -50% -80% -100% Heckmann 2016 Heckmann Rathinasabapathy 2016 2018 Rathinasabapathy Choe 2010 2018 Thalidomide is comparable to the best drugs in reducing the fibrosis score in the bleomycin model 33

Cough VAS Cough VAS IMiDS ARE EFFECTIVE IN IPF COUGH 100 p<0.001 100 80 80 60 60 2012 In a double-blind crossover study, thalidomide had a dramatic effect on cough frequency 40 20 40 20 Unlike other chronic cough, IPF do not respond to placebo treatment 0 End of Period 1 Placebo End of Period 2 Thalidomide 0 End of Period 1 Thalidomide End of Period 2 Placebo Reduction of cough is a unique feature of IMiDS 34

IMiDS IMPROVE QUALITY OF LIFE IN IPF Quality of life, as measured by the specific St George s Respiratory Questionnaire (SGRQ), is improved by IMiD treatment An absolute change of 4 is considered clinically relevant Change in SGRQ scores 10 2012 Δ Improvement 0 No other approved or investigational drug even shows stabilization of SGRQ Thalidomide 12 w; n=20 D=11.2; p=0.001 Nintedanib 52 w; n=700 and 500 D=2.05; p=0.0095 10 Δ Deterioration IMiDS are the only drug class that improves quality of life 35

DRUG FORMULATION IMiDs in amorphous form are loaded in nanopores of biodegradable microspheres After lung deposition there is an immediate release of 30% and a sustained release of the remaining 70% as the microspheres degrade By loading biodegradable microspheres, IMiDs can be delivered in solution to the lung tissue Pulmonary delivery is expected to reduce systemic exposure by 50-85% 37

IMiDS IN FIBROTIC LUNG DISEASE LUNG TISSUE INTERSTITIAL FIBROSIS FIBROTIC MEDIATORS STRETCH ACTIVATION COUGH IMPROVED QoL LUNG RESISTANCE VESSEL FIBROTIC MEDIATORS VASCULOPATHY IMPAIRED GAS EXCHANGE HYPOXIA VASOCONSTRICTION DYSPNOEA PH/HEART FAILURE INCREASED SURVIVAL IMiDS reduce fibrosis and severe cough 38

39 MARKET

Million THE IPF MARKET Global sales by brand $1 250 Combined global sales surpassed US $1.9 billion in 2017 $1 000 $750 Price for one year s treatment is close to $100,000 $500 $250 $0 2014 2015 2016 2017 2018e Company reports, Bloomberg Esbriet (pirfenidone) Ofev (nintedanib) 75% of the sales are in the US GlobalData estimates annual sales of $3.2 billion in 2025 40

41 SUMMARY

CREATING A LEADING FIBROTIC LUNG DISEASE COMPANY VP01 (C21) Reduces fibrosis Effects on vasculopathy and pulmonary hypertension VP02 (IMiD) Reduces cough and improves QoL Reduces pulmonary sarcoidosis Systemic delivery Targeted to the lung 42

COMBINED PIPELINE 2018 2019 2020 2021 VP01 (C21) IPF SECOND INDICATION PHASE I (dosing) FORMULATION PHASE IIa (TBD) PHASE II (pilot) PHASE I (bridging) NEW CHEMISTRY PIVOTAL PHASE II/III IPF Preparations PHASE II 2nd indication VP02 (IMiD) IPF/COUGH SECOND ILD FORMULATION TOX PHASE I PHASE II IPF/COUGH PHASE II 43

SUMMARY FOCUS ON PATIENTS WITH FIBROTIC LUNG DISEASE TWO UNIQUE AND DIFFERENTIATED DEVELOPMENT PROGRAMMES CAN ADDRESS SEVERAL ILDs IN PARALLEL ORAL AND LOCAL DELIVERY HIGHLY EXPERIENCED TEAM 44