BRAINco Biopharma company presentation

2. BRAINco Biopharma
Context and Background

3. PROGENIKA GROUP
Progenika Group BRAINco Biopharma
is part of the Pioneer in Personalized Develops and commercializes products
Progenika Group of Medicine with diagnostic for personalized treatments for
companies.
products for complex diseases of the nervous system.
genetic diseases.
 Progenika Group is composed by seven companies, including Progenika Inc in Boston and Progenika
Latam in Mexico to introduce Progenika products in USA and Latin America.
 Proteomika, Preventia, Abyntek are other companies part of Progenika Group.

4. BRAINco Biopharma
History
2008 – Schizophrenia and Major Depression Projects
 Progenika´s internal research identified, through proteomic and genomic studies, alterations in the
expression 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 drug
discovery with the creation of BRAINco Biopharma.
 BRAINco set up two drug discovery programs, in which cellular and animal models were generated and
characterized in order to validate the target, as well as for their use all along the drug discovery programs and
lead optimization.
2010- Multiple Sclerosis Project
 BRAINco in-licensed molecules from the Spanish Research Council and started a new project in Multiple
Sclerosis based on a new mechanism of action relevant for the disease.

5. BRAINco Biopharma
WORKING 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 based
on innovative targets found altered in the diseases.
 BRAINco optimizes treatments through the BRAINco
Biopharma
development of biomarker discovery programs.
KOLs in Research
the field centers
Pharmacogenomic tools:
 The company also develops and commercializes
pharmacogenomic tools. BRAINco designs, develops and generates tools
for drug discovery programs.

6. WORKING MODEL
Where are “our labs”?
BRAINco Collaborations

7. BRAINco Biopharma
Drug Discovery

8. BRAINco Biopharma
Drug Discovery
Target Assay Target Hit Hit to Lead Preclinical Clinical
Discovery 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, Regulatory
Internal  Security,
screening assays
evaluation  PK/PD.
Biochemical In silico Virtual Hit validation:
assays modeling screening In-vitro
testing
Biomarker discovery

9. DRUG DISCOVERY: Major Depression
A 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

10. DRUG DISCOVERY: Major Depression
A 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.

11. DRUG DISCOVERY: Schizophrenia
Neurotransmitter release and Schizophrenia
 BRAINco found that a specific protein, involved in the neurotransmitter release, was significantly
overexpressed in the prefrontal cortex of schizophrenic suicides. Other research groups also found that the
target and proteins of the basic exocytosis machinery were differently expressed in the brain of subjects
with Schizophrenia and other psychiatric diseases.
 The neurotransmitter release machinery is a
very promising mechanism of action for the
development of new drugs in Schizophrenia, due
to its direct implication in several processes found
altered in this disease:
 Neurotransmission,
 Neurite outgrowth and connectivity,
 Receptor/Transporter translocation.
BRAINco is targeting a new mechanism of action found altered in the disease.

12. DRUG DISCOVERY: Schizophrenia
Neurotransmitter release and Schizophrenia
 The target and other proteins from the basic neurotransmitter release machinery have been found
altered 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.

13. DRUG DISCOVERY: Multiple Sclerosis
PDE7 and Multiple Sclerosis
 PDE7 regulates intracellular levels of cyclic adenosine
monophosphate (cAMP).
cAMP AMP
 cAMP, apart from its role in the regulation of the immune
PDE7
system, it is also involved in a wide range of neuronal
functions, including neuroprotection and neuroinflammation.
 PDE7 enzyme is expressed in immune and pro-inflammatory
cells, as well as in the brain. Recent data showed an upregulation in PDE7
inhibitors
the central nervous system of PDE7A and PDE7B proteins associated
to neuroinflammation in an experimental model of Parkinson Anti-Inflammation
disease. Neuroprotection
Neurogenesis
 It has been recently described that PDE7 inhibitors confer
protection against alteration of neuron´s morphology in the spinal
cord 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.

14. DRUG DISCOVERY: Multiple Sclerosis
PDE7 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 also
promote 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.

15. DRUG DISCOVERY
Biomarkers and patient selection
A biomarker program is set up once first molecules are found and start being optimized. All the tools
developed 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 other
pathologies, such as cancer.
 Alterations in the expression of the target in the animal model, as well as in patients, are being
investigated 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 by
current drug treatments have been selected by BRAINco´s team.
 Protocols to measure these biomarkers at mRNA and protein levels in different tissues/fluids, are being
optimized.

16. 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

17. BRAINco Biopharma
Pharmacogenomic tools

18. BRAINco Biopharma
Pharmacogenomic 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.

19. BRAINco Biopharma
Brainchip, Available on the market
BRAINchip I detects the genetic variations of
CYP450 enzymes, which metabolize most antidepressant
and antipsychotic drugs, providing information about :
 Optimal antipsychotic and antidepressant drug for
each patient,
 Interaction with concomitant drugs undergoing the
same metabolic pathways.
Brainchip Increases safety and efficacy of
antidepressant and antipsychotic drug treatments, as well
as treatment adherence rates.
Approximately 10% of the population has a slow acting
form of this enzyme and 7% a super-fast acting form.

20. Pharmacogenetic products
Market strategy
BRAINco commercializes its pharmacogenomic products through a global network of distributors.
Norway Sweden
Finlande
Austria
Turkey
Spain Middle east
Egypt
Mexico
BRAINchip distributors

21. BRAINco Biopharma
Intellectual Property

22. DRUG DISCOVERY: IP and publications
Patents
 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)

23. Thank you for your attention.
Julie Masse
www.brainco.es Business Development Manager
jmasse@brainco.es
Jose Mª Palacios
Director of Research and Development
jmpalacios@brainco.es
BRAINco Biopharma, S.L.
Bizkaia Technology Park. Building 504
48160 Derio (Spain)
www.brainco.es
Phone: +34 94 406 4525