PROGENIKA GROUP Progenika Group BRAINco Biopharmais part of the Pioneer in Personalized Develops and commercializes productsProgenika Group of Medicine with diagnostic for personalized treatments forcompanies. products for complex diseases of the nervous system. genetic diseases. Progenika Group is composed by seven companies, including Progenika Inc in Boston and ProgenikaLatam in Mexico to introduce Progenika products in USA and Latin America. Proteomika, Preventia, Abyntek are other companies part of Progenika Group.
BRAINco BiopharmaHistory2008 – Schizophrenia and Major Depression Projects Progenika´s internal research identified, through proteomic and genomic studies, alterations in theexpression levels of several genes and proteins in the brain of Schizophrenic and Depressed subjects(suicides). After IP research and market study, Progenika identified a great opportunity and decided to get into drugdiscovery with the creation of BRAINco Biopharma. BRAINco set up two drug discovery programs, in which cellular and animal models were generated andcharacterized in order to validate the target, as well as for their use all along the drug discovery programs andlead optimization.2010- Multiple Sclerosis Project BRAINco in-licensed molecules from the Spanish Research Council and started a new project in MultipleSclerosis based on a new mechanism of action relevant for the disease.
BRAINco BiopharmaWORKING MODEL: Professional Project Management drives the process OPEN INNOVATION MODEL Developing Innovative Personalized Treatments for CNS diseases through the integration of Scientific Excellence and Industrial Drive.Drug Discovery: CROs BRAINco carries out drug discovery projects basedon innovative targets found altered in the diseases. BRAINco optimizes treatments through the BRAINco Biopharmadevelopment of biomarker discovery programs. KOLs in Research the field centersPharmacogenomic tools: The company also develops and commercializespharmacogenomic tools. BRAINco designs, develops and generates tools for drug discovery programs.
WORKING MODELWhere are “our labs”? BRAINco Collaborations
BRAINco BiopharmaDrug DiscoveryTarget Assay Target Hit Hit to Lead Preclinical ClinicalDiscovery Development Validation Finding Lead Optimization Evaluation Evaluation Major Depression project Multiple Sclerosis project Animal Screening model cascade:Post mortem Schizophrenia project Potency,studies Target validation Efficacy in Cell based High Hit validation: animal model, Preclinical assays throughput Cell based ADMEtox, RegulatoryInternal Security, screening assaysevaluation PK/PD. Biochemical In silico Virtual Hit validation: assays modeling screening In-vitro testing Biomarker discovery
DRUG DISCOVERY: Major DepressionA cytokine as new target for Major Depression Studying post-mortem brain tissues, BRAINco found that a specific cytokine, involved in neurogenesis and synaptogenesis, was significantly overexpressed in the prefrontal cortex of major depressive subjects. DEPRESSION The target is a secreted cytokine. ALTERATIONS IN: The target induced responses are BRAIN PLASTICITY BRC target SYNAPTOGENESIS mediated by different receptors. NEUROGENESIS NEUROTRANSMISSION BEHAVIOR & COGNITION BRAINco findings have shown, for the first time, a direct implication of this cytokine and its related biological system in Major Depression, which represents a very promising mechanism of action for drug development of new and more efficacious antidepressants
DRUG DISCOVERY: Major DepressionA cytokine as new target for Major Depression Transgenic mice overexpressing the target could be considered a non classical model of depression: At basal state, TG mice present an anxious-like phenotype, cognitive impairment and alterations in brain plasticity (Neurogenesis and LTP). After an aversive stimulus, TG mice show a higher sensitivity to develop a depressive-like phenotype. Chronic antidepressant treatment reverses both, anxious and depressive symptoms. Human neuronal progenitor cell models have been selected for cell based assays. Changes in neurogenesis properties have been confirmed in these models. Lead compounds acting on target-associated signaling pathways are available. The target is a secreted cytokine that can be measured in human serum, making the development of specific biomarkers easier and very feasible. BRAINco proposes a project based on an innovative target system with a novel mechanism of action. Our results suggest that BRAINco target could allow the finding of molecules for the treatment of a specific subtype of the disease: Anxious Depression.
DRUG DISCOVERY: SchizophreniaNeurotransmitter release and Schizophrenia BRAINco found that a specific protein, involved in the neurotransmitter release, was significantlyoverexpressed in the prefrontal cortex of schizophrenic suicides. Other research groups also found that thetarget and proteins of the basic exocytosis machinery were differently expressed in the brain of subjectswith Schizophrenia and other psychiatric diseases. The neurotransmitter release machinery is avery promising mechanism of action for thedevelopment of new drugs in Schizophrenia, dueto its direct implication in several processes foundaltered in this disease: Neurotransmission, Neurite outgrowth and connectivity, Receptor/Transporter translocation. BRAINco is targeting a new mechanism of action found altered in the disease.
DRUG DISCOVERY: SchizophreniaNeurotransmitter release and Schizophrenia The target and other proteins from the basic neurotransmitter release machinery have been foundaltered in the brain of subjects with Schizophrenia as well as other psychiatric diseases. BRAINco used two approaches to find molecules: Cell based approach, to find molecules that modulate exocytosis in specific human neuronal cell lines that overexpressed the target. Target focused approach, to find molecules that break the liaison between the target and its ligand. Chemical starting points, modulating neurotransmitters release, have been identified. BRAINco is going to test best molecules coming from both approaches: cell based assays and animal model. An animal model overexpressing the target has been generated, it presents schizophrenia characteristics: morphological alteration of the brain, as well as specific positive, negative and cognitive symptoms. BRAINco has discovered molecules acting on an innovative target which controls neurotransmitter release. BRAINco molecules could become a novel and promising treatment for Schizophrenia. Targeting the exocytosis opens a wide range of possibilities in terms of indications.
DRUG DISCOVERY: Multiple SclerosisPDE7 and Multiple Sclerosis PDE7 regulates intracellular levels of cyclic adenosinemonophosphate (cAMP). cAMP AMP cAMP, apart from its role in the regulation of the immune PDE7system, it is also involved in a wide range of neuronalfunctions, including neuroprotection and neuroinflammation. PDE7 enzyme is expressed in immune and pro-inflammatorycells, as well as in the brain. Recent data showed an upregulation in PDE7 inhibitorsthe central nervous system of PDE7A and PDE7B proteins associatedto neuroinflammation in an experimental model of Parkinson Anti-Inflammationdisease. Neuroprotection Neurogenesis It has been recently described that PDE7 inhibitors conferprotection against alteration of neuron´s morphology in the spinalcord from spinal cord injury mouse models. The control of cAMP levels by PDE7 inhibitors may play a crucial role in the development of neuroinflammatory associated diseases, such as Multiple Sclerosis. BRAINco has synthesized several families of PDE7 inhibitors.
DRUG DISCOVERY: Multiple SclerosisPDE7 and Multiple Sclerosis More than a hundred new compounds have been chemically synthesized. PDE7 IC50 is in the nM range. Molecules present selectivity for PDE7. Compounds are orally available and cross the blood brain barrier. Molecules present neuroprotective and anti-Inflammatory activities in cellular models. They alsopromote neurogenesis. After administration of BRAINco compounds, the clinical score in two well established Multiple Sclerosis animal models is significantly improved. Anti-inflammatory and neuroprotective properties of the compounds have been confirmed in tissues from these animal models. Biomarker program is ongoing BRAINco has developed specific inhibitors for PDE7 enzyme. Their anti-inflammatory, as well as neuroprotective activities have been demonstrated in vivo and in vitro. All these results support the development of new Multiple Sclerosis treatments based on BRAINco PDE7 inhibitors.
DRUG DISCOVERYBiomarkers and patient selectionA biomarker program is set up once first molecules are found and start being optimized. All the toolsdeveloped during hit validation and hit finding will be used for biomarker discovery.Major Depression BRAINco target is secreted and the protein can be measured in serum of patients with otherpathologies, such as cancer. Alterations in the expression of the target in the animal model, as well as in patients, are beinginvestigated using non-invasive samples.Schizophrenia Exocytosis can be measured in several peripheral tissues. Results obtained with the animal model will be used for a biomarker discovery program.Multiple Sclerosis Specific cytokines, as well as other specific markers altered in Multiple Sclerosis and modulated bycurrent drug treatments have been selected by BRAINco´s team. Protocols to measure these biomarkers at mRNA and protein levels in different tissues/fluids, are beingoptimized.
DRUG DISCOVERY:Business Model In order to bring these novel molecules to patients, BRAINco is looking for partners: Investors and/or Companies. Target Target Hit Hit to Lead Preclinical Clinical Discovery validation Finding Lead Optimization Evaluation Evaluation Major Depression 2015 Schizophrenia 2014 Multiple Sclerosis 2015 Completed activities Activities under development
BRAINco BiopharmaPharmacogenomic products Pharmacogenomics is the study of DNA genetic variations which can lead to changes in drug response. DNA Single Nucleotide Polymorphisms (SNP) related to drug metabolism, drug transporters, and drug targets are Offers tools based on responsible for variations in the efficacy and/or toxicity of many drugs. DNAchip technology. The use of pharmacogenomics in routine clinical practice leads to: Increase drug safety and efficacy. Increase drug treatment adherence. Decrease direct and indirect costs of the disease.
BRAINco BiopharmaBrainchip, Available on the marketBRAINchip I detects the genetic variations ofCYP450 enzymes, which metabolize most antidepressantand antipsychotic drugs, providing information about : Optimal antipsychotic and antidepressant drug foreach patient, Interaction with concomitant drugs undergoing thesame metabolic pathways. Brainchip Increases safety and efficacy ofantidepressant and antipsychotic drug treatments, as wellas treatment adherence rates. Approximately 10% of the population has a slow acting form of this enzyme and 7% a super-fast acting form.
Pharmacogenetic products Market strategyBRAINco commercializes its pharmacogenomic products through a global network of distributors. Norway Sweden Finlande Austria Turkey Spain Middle east Egypt Mexico BRAINchip distributors
DRUG DISCOVERY: IP and publicationsPatents STXBP1 as psychiatric biomarker in murine model system and their uses. WO/2010/020642. Compound that is a dual inhibitor of enzymes PDE7 and/or PDE4, pharmaceutical compositions and uses thereof. WO/2008/113881. A genotyping tool for improving the prognostic and clinical management of MS patients. WO/2010/103292. Animal model for OMTX-MDT1: psychiatric marker, System Model and Related Methods (provisional patent application).Publications María José Guerrero, Itsaso Hormaeche, María Uribarri, Julie Masse and José María Palacios “The exocytosis machinery as a target for the development of new drugs for Schizophrenia“ in Luis M. Botana and Mabel Loza “Therapeutic Targets: Modulation, Inhibition and Activation“. 2012.“ Brain over expression of munc18-1a in mice induces a schizophrenia-related phenotype”, 2012. (Submitted)
Thank you for your attention. Julie Massewww.brainco.es Business Development Manager firstname.lastname@example.org Jose Mª Palacios Director of Research and Development email@example.com BRAINco Biopharma, S.L. Bizkaia Technology Park. Building 504 48160 Derio (Spain) www.brainco.es Phone: +34 94 406 4525