What is Iproteos? Biotech. Results so far Spin-off. Cutting-edge PEPTIDE Technology. Early R&D. Focus on CNS

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2 What is Iproteos? Biotech Results so far Spin-off Cutting-edge PEPTIDE Technology Early R&D Focus on CNS

3 Core Team Dr. Teresa Tarragó Co-founder & CEO Research Associate IRB ESADE EMBA 2012 > 15 years drug development Dr. Roger Prades Head of Pre-clinical Development > 10 years experience Experience in pre-clinical development and BBB Dr. Soledad Royo Dr. Jesus Seco Head of Medicinal Chemistry > 10 year experience Peptide Chemistry & IP Bielefeld University (Germany) Head of Computational Chemistry > 5 year experience Computer-based drug design University of Oklahoma (USA)

4 Scientific Advisory Board Prof. Ernest Giralt Co-founder & Chairman of SAB Full professor of Organic Chemistry in the UB Dir. Chemistry and Molecular Pharmacology- IRB Barcelona Premio Nacional de Investigación 2011, MICINN Novartis Chemistry Lecturer, patents registered & 3 start-up projects & 400 papers Dr. Catia Teixeira Advisor Neurobiology Molecular basis of behavior, cognition and psychiatric diseases > 15 years experience Sick Kids Hospital (University of Toronto), (IRB Barcelona), and currently at Columbia University.

5 Achievements so far Consortium Framework Programme Seven (FP7) as SME Neotec-CDTI Awards Joven Emprendedor en Biotecnología SEBBM, 2011 Red Emprendia University to Business Competition second prize Finalist of the BIOCHEM BP Competition Frankfurt One patent to be submitted to the European Patent Office (EPO)

6 FROM PROTEASES TO PEPTIDE DRUGS Central Nervous System Diseases

7 *Source: SCRIP Business Insights R & D Market Central Nervous System (CNS) One of the largest and fastest growing markets The main indications in the CNS market are depression/major depressive disorder, schizophrenia, bipolar disorder, Alzheimer's disease, attention deficit hyperactivity disorder and migraine. 13% of the population is affected by a CNS disorder (there are more than 600). The number is expected to grow until a 14.2% of the population by 2020 Global CNS market 71.4 billion $ in 2010 UNMET MEDICAL NEEDS

8 CNS diseases Alzheimer Schizophrenia Parkinson Epilepsy Bipolar Disorder Global CNS market 71.4 billion $ in 2010

9 The Blood-Brain Barrier (BBB) 98 %

10 Current drugs: sticky small molecules Unspecific = SIDE-EFFECTS

11 From proteases to peptide drugs Target types Ligand types COMPACT BINDING EXTENDED BINDING Protein - Protein Interactions Proteases Phosphatases Kinases GPCRs/ Aminergic Receptors Small molecule drugs Peptides Proteins/MAbs Biologics

12 FROM PROTEASES TO PEPTIDE DRUGS Proteases and Protein-protein interactions (PPIs) as drug targets

13 Proteases as drug targets > 700 Human Proteases identified Implicated in almost every disease Over 5-10 % of all pharmaceutical targets in drug development DIFFICULT TO ADDRESS BY CONVENTIONAL METHODS

14 FROM PROTEASES TO PEPTIDE DRUGS IPRO TM Technology

15 Iproteos technology, IPRO TM Platform for drug design & evaluation & optimization CNS permeability optimization

16 Peptides as drugs for PPIs Target specificity Low toxicity Low side-effects Low immunogenicity Chemically affordable

17 Therapeutic Peptide Market Growth CNS therapeutic peptide market potential is immense CAGR: Compound Annual Growth Rate in $ Source: Bionest Partners

18 Approved peptide pharmaceuticals >60 First Generation Second Generation New Generation Oxytocin ACTH (1-24) & (1-39) Vasopressin Insulin Glucagon Calcitonins TRH Gonadorelin Somatostatin GHRH (1-29) & (1-44) CRF (Human & Ovine) Cyclosporin Thymopentin Thymosin Alpha-1 Secretins (Human & Porcine) Parathyroid Hormone (1-34) & (1-84) Vasoactive Intestinal Polypeptide Brain Natriuretic Peptide Cholecystokinin Tetragastrin Pentagastrin Eledoisin Carbetocin Terlipressin Felypressin Buserelin Deslorelin Goserelin Histrelin Leuprolide Nafarelin Tryptorelin Lecirelin Lanreotide Octreotide Atosiban Desmopressin Lypressin Ornipressin Pitressin ACE Inhibitors (Enalapril, Lisinopril) HIV Protease Inhibitors Abarelix Cetrorelix Ganirelix Integrilin Bivalirudin Copaxone Techtide P-289 Cubicin Fuzeon Ziconotide Pramlintide Exenatide Icatibant Degarelix Liraglutide Dr Mike Verlander, Asia TIDES, Tokyo (2009)

19 FROM PROTEASES TO PEPTIDE DRUGS Pipeline

20 IPRO001 Cognition Enh. Discovery POC & Preclinical Ph I 1 st License IPRO002 Alzheimer IPRO003 Epilepsy Discovery X Discovery POC / Preclinical POC / Preclinical Ph I 2 nd L IPRO004 Parkinson POC / Preclinical Ph I FFFs VC Ingresos 110K 2 M IPRO001 & IPR004 European patent application VC INNCORPORA - NEOTEC I - FP7 1% of the American population and 0.4% of the European 4 Préstamos millions & affected Subvenciones in 2016 Prest & Sub

21 FROM PROTEASES TO PEPTIDE DRUGS Schizophrenia

22 Symptoms and treatment 1%-0.4% population (4 M people will be affected in 2016) Antipsychotic drugs Sales 4 billion $ in 2010 MEDICAL NEED COGNITIVE ENHANCER

23 Brain protease-> Peptide cognitive enhancer INHIBITORS -> COGNITION ENHANCING EFFECTS

24 Hit to lead -> Lead optimization -> POC 1 Protease Inhibition (in vitro & cells) 2 BBB permeability (PAMPA &Caco 2) 3 Stability (human serum,microsomes ) 4 Toxicity (MTT, zebrafish embryos, ) 5 Preclinical Proof-of-concept (water maze, open field )

25 Protease inhibition: potency & specificity Fluorescence protease assay Compound IC50 (nm) ± SD Target Protease Protease 2 (µm) Protease 3 (µm) IPR ± 55 > 400 > 400 IPR ± 72 > 400 > 400 IPR49 64 ± 11 > 400 > 400 IPR50 60 ± 10 > 400 > 400 IPR53 48 ± 21 > 400 > 400

26 BBB permeability PAMPA Caco-2 Compound Pe (x10-6 cm/s) % Transport IPR19 4,29 ± 1,1 8,24 ± 1,9 IPR25 7,28 ± 2,7 13 ± 4,4 IPR49 22,13 ± 5,8 29,9 ± 4,8 Compound Pe (x10-5 cm/s) % Transport A/B ratio B/A ratio IPR19 1,46 ± 0,4 3,86 ± 0,9 0,38 4,54 IPR25 1,14 ± 0,02 3 ± 0,05 0,2 23,54 IPR49 2,15 ± 0,4 5,69 ± 1,14 0,52 0,72

27 Stability Human serum: Compound IPR19 IPR25 IPR49 Half-life time (24h) > 24h > 24h > 24h

28 Toxicity 1. MTT: 2 neuroblastoma cell lines No toxicity observed up to 500 µm 2. Zebrafish embryos -> acute toxicity (10 to 200 µm) Compound IPR25 IPR49 Toxicity No sign No sign 3. Mice -> acute toxicity in progress (30 mg/kg no signs)

29 Preclinical Proof-of-Concept Water maze C57/bl6 wt mice and schizophrenic model mice Open field Object recognition Passive avoidance

30 POC -> Passive avoidance GREEN = CONTROL BLUE = IPR49

31 Leading the future

32 FROM PROTEASES TO PEPTIDE DRUGS Thank you