www.iproteos.com Corporate Presentation November, 2013
The company Iproteos is an early-stage drug development company founded in 2011: Spin-Out from Institute for Research in Biomedicine (IRB Barcelona) and University of Barcelona (UB). Based in Barcelona, Spain. Strong expertise in Drug Discovery and Project Management. Aimed at developing new therapies for CNS diseases with special focus in Schizophrenia, Epilepsy and Parkinson s disease through an innovative approach: protein-protein interactions (PPIs) and therapeutic peptides. Iproteos has raised 0,8 M in public and private funding.
Founders and Managing Team Teresa Tarragó, PhD, MBA Co-founder and CEO of Iproteos PhD in Biology by the University of Barcelona, Research Associate at IRB and Executive MBA from ESADE Business School. More than 15 years of professional experience in the field of drug discovery, working on Protein-Protein Interfaces (PPIs), Central Nervous System (CNS) and also leading research teams. Inventor of 2 patents. Collaborations with other biotech companies, such as Farmhispania and Intelligent Pharma.
Founders and Managing Team Ernest Giralt, PhD, Prof. Co-founder & Chairman of Scientific Advisory Board (SAB) Professor of Organic Chemistry Department at University of Barcelona and Head of the Chemistry and Molecular Pharmacology Programme at Institute for Research in Biomedicine where he leads his own research group. With more than 30 years experience in peptide synthesis and biomedical problems, is considered Key Opinion Leader (KOL) in the field of therapeutic peptides and Protein- Protein Interfaces (PPIs). He has been awarded with prestigious Novartis Chemistry Lecturer (2011) He has published more than 140 scientific articles and inventor of 10 patents about therapeutic peptides. Member of advisory boards for pharma or biotech companies, such as: SOM Biotech and Intelligent Pharma.
Advisory Board Iproteos has established an advisory board with proven experience in different CNS-related fields. His members, besides Co-founder Ernest Giralt, are: Catia Teixeira, PhD Advisor in Neurobiology Researcher at Columbia University, she has a broad experience in behavioral neuroscience. More than 15 years experience in molecular basis of behavior, cognition and psychiatric diseases in top Research Institutes. J. Javier Meana, MD, PhD, Prof. Advisor in Pharmacology and Schizophrenia Professor of Pharmacology at the University of the Basque Country (UPV/EHU) where he holds the leadership of the Neuropsychopharmacology Group. With large experience in pharmacology and neurobiology. He received in 2009 the Spanish national award to research in Biological Psychiatry.
Network & SAB & Key Opinion Leaders Poland India, Prima International
FROM PPIs TO PEPTIDE DRUGS Protein-protein interactions (PPIs) as drug targets & peptides as drugs
Protein-protein Interactions (PPIs) -> Drug targets of the future PPIs > 300.000.000 potential PPIs > 300.000 known > 80.000 druggable (Dr. PIAS DataBase, Database, Vol. 2012) Implicated in almost every disease DIFFICULT TO ADDRESS BY CONVENTIONAL METHODS (Small molecules-> too unspecific; Biologics -> can not reach brain)
From PPIs to peptide drugs Unlike drug-like molecules or biological macromolecules, peptides represent an intermediate and ideal hybrid stage to suitably address challenging protein targets, such as PPI s and Proteases PPI s Proteins/MAbs Biologics Target types Proteases Phosphatases Kinases GPCRs/ Small molecule drugs Peptides Peptides Aminergic Receptors Ligand Complexity / Properties
Peptides -> drugs of the future to target PPIs Target specificity Low toxicity Low side-effects Low immunogenicity Chemically affordable
Therapeutic Peptide Market Growth CNS therapeutic peptide market potential is immense CAGR: Compound Annual Growth Rate in $ Source: Bionest Partners
FROM PPIs TO PEPTIDE DRUGS Iproteos Cutting-edge solution: IPRO Technology & IPRO Peptides
IPRO technology Platform for drug design & evaluation & optimization of peptides Biologic Assays Structurebased Drug design ADME Evaluation Lead Selection Lead Optimization Lead Candidate Toxicology Assays Permeability optimization of peptides
IPRO tech: From computational design Hit > 250,000 in silico evaluated peptide compounds 100 Best Candidates selected Hit < 20 Best Peptides Evaluated < 20 Best Peptides Synthesized
Computational Toolbox specifically designed for peptides Atlas Generates thousands of soluble peptide structure combinations. Empirical rules based on synthetic feasibility. Key factors which favor membrane permeability. Canvas Identifies either allosteric or protein-protein binding sites of protein targets according to their 3D-structure. Provides valuable information to guide Atlas in the peptide generation process and in the hit-to-lead optimization stage. Dante Dante is an integrated receptor-based virtual screening workflow to identify active molecules based on the information coming from Atlas and Canvas.
Advantages of IPRO peptides Drug Properties Small Molecules Biologics Natural Peptides IPRO Peptides Specificity + +++ ++ +++ Permeability to GIT and BBB +++ -- + ++ Plasma Stability +++ + -- +++ Toxicity Medium Low Low Low Immunogenicity - +++ + - Cost of manufacturing
FROM PPIs TO PEPTIDE DRUGS Business Model
Business model Partnership agreements Partnership agreements with pharmaceutical and biotech companies to exploit the advantages of IPRO technology. Projects targeting intracellular PLIs or PPIs. Enhancement of ADME properties of peptidomimetics. Co-development for our pipeline candidates. Out-licensing Iproteos proprietary pipeline is currently focused on CNS related-diseases. First-in-class cognitive enhancer for the treatment of the cognitive symptoms associated with schizophrenia. Current state: Ready for out-licensing. Preventive treatment of Parkinson s disease. Current state: Preclinical PoC. Preventive and curative treatment of epilepsy. Current state: Lead optimization.
FROM PPIs TO PEPTIDE DRUGS Validated technology
FROM PPIs TO PEPTIDE DRUGS SUCCESS CASE Cognitive enhancement: An innovative approach for Schizophrenia (CIAS)
Schizophrenia Market 1%-0.4% population (4 M people will be affected in 2016) Antipsychotic drugs Sales 4 billion $ in 2010 CIAS: MEDICAL NEED COGNITIVE ENHANCER
Iproteos Product IPR-088 Small peptidomimetic Targeting Cognitive Impairment Associated with Schizophrenia First-in-Class: novel Mechanism of Action Development Status: Pre-clinical Proof-of-Concept; IND Q2 2015 IPR-19
Highlights of IPR-088 Efficacy Chemistry Survival assay in vitro Preclinical PoC in three well-established pharmacological animal models of schizophrenia A simple, short and efficient synthesis has been successfully developed ADME & PK IPR-088 crosses the Blood-Brain Barrier and reaches the CNS Toxicology Animals tolerated IPR-088 even at high doses (30 mg/kg) Animals did not show either abnormal behavior or weight loss
PoC in wt animals Morris Water maze Test Mice treated with IPR-088 display memory enhancement over time Control Mice IPR-19 IPR-088 treated mice
PoC in wt animals Morris Water maze Test Mice treated with IPR-088 display memory enhancement over time 40 Time in quadrant (%) 30 20 10 0 Control IPR19
PoC in wt animals Passive avoidance Control IPR-088 IPR-19
Preclinical PoC in validated models of schizophrenia Acute studies conducted in: - MK801 model in C57/bl6 J mice (MK801 acute administration) - Phencyclidine model in C57/bl6 J mice (Phen chronic administration) - Immunochemical challenge with poly (I:C) in C57/bl6 J mice (acute treatment in pregnant mice) Tested in: - Object recognition - T-maze - Radial arm maze - Water maze - Passive avoidance IPR-19
Development Plan for IPR-088 Preclinical Package ADME studies Toxicology Planned Ongoing Toxicological studies: 2 species Q1 2014 Genotoxicity (2 studies) Done Safety Pharmacology Q3 2014 The preclinical package is expected to be completed by Q1 2015 IND submission Q2 2015 DEVELOPMENT Clinical Trials PLAN Planned to STATUS start by Q3 2015 A phase I study planned First Patient In (FPI) Q3 15
Competitors IPR-19 May 2013
FROM PPIs TO PEPTIDE DRUGS Targeting Epileptogenesis: Towards a curative treatment of Epilepsy
Epilepsy market ~ 30 % patients do not respond to treatment Current inhibitors are palliative anti-epileptic drug, but they do not target epileptogenesis
Brain protein. Role in epileptogenesis Target involved in epileptogenesis is challenging and highly similar to other members of protein family (protein B, C, D..). No selectivity achieved so far for this target!!
IPRO tech: From computational design Hit > 250,000 in silico evaluated peptide compounds 100 Best Candidates selected Hit < 20 Best Peptides Evaluated < 20 Best Peptides Synthesized
IPRO tech: From computational design Hit Compound Protein A Protein B IPR-67 569 nm 691 nm IPR-68 6,400 nm 172 nm IPR-69 > 10,000 nm 313 nm IPR-79 1,400 nm 1,600 nm IPR-96 328 nm > 3,000 nm Target involved in epileptogenesis is Protein A. Protein B is a highly homologous protein for which non selective drugs have been obtained so far A selective drug has already been obtained by Iproteos.
Development Plan for IPR96 ADME optimization & Preclinical PoC Preclinical Package Planned Toxicology ADME optimization Q4 2013 PoC Epilepsy animal models Q2 2014 Planned ADME studies Q4 2014 Toxicological studies: 2 species Q1 2015 Genotoxicity (2 studies) Q4 2014 Safety Pharmacology Q1 2015 The preclinical package is expected to be completed by Q2 2016 IND submission Q3 2016
FROM PPIs TO PEPTIDE DRUGS Iproteos C/ Baldiri Reixac, 10 08028 Barcelona, Spain T. (+34) 934 020 906 www.iproteos.com info@iproteos.com