Collaborazione tra Università e Industria in un progetto europeo "Innovation 2" del Settimo Programma Quadro

(FP7): THINPAD

Salute in Horizon 2020:

Giornata Nazionale di Lancio dei bandi 2014-15

- Maurizio Botta -

Università degli Studi di Siena

3 Dicembre 2013, Roma

Prof. Maurizio Botta

- 1974. Laurea cum laude in Chemistry at University of Rome - 1979. PhD Università del New Brunswick, Canada (Prof. Wiesner) - 1980-1985 Researcher at University of Rome (Prof. Nicoletti) - 1985-87. Post-doc at Montreal (Prof. Hanessian) - 1987 Professore Associato, University of Siena -2000 Professore Ordinario, University of Siena -- Member Editorial board of ACS J. Med. Chem., ChemMedChem -- Adjunt Professor Sbarro Institute for Cancer Research and Molecular Medicine Temple University, Philadelphia, USA

Google scholar CITATION REPORT

Number of publications: 430 Number of Patents: 15

Number of citations: 5917 h-index: 37

i10-index: 210

University of Siena

Dipartimento di Biotecnologie, Chimica e Farmacia

-Polo Scientifico San Miniato –

Via Aldo Moro 2 53100 - SIENA, Italy

The Dipartimento di Biotecnologie, Chimica e Farmacia of Siena University was

created in 1982. It is situated within the Scientific Area of the San Miniato

University Campus, where the majority of the scientific and educational

institutions are housed and where to it moved in 1999 from its previous location

at the centre of Siena.

Disease

selection

Gene to

function

Function

to Target

Target to

Hit

Hit to

Lead

Lead

optimisa-

tion

Pre-dev.

compound Phase I Phase II Phase III Phase IV

milligrams grams kilos

Combined application of Molecular Modeling , Combinatorial Chemistry and Analytical

Techniques to Speed-up the Lead Discovery Process

Molecular Modeling

Primary libraries

Focused libraries

Combinatorial Chemistry

Solid-phase synthesis

Parallel synthesis

Asymmetric synthesis

Biotransformation using enzymes

Microwave-assisted synthesis

Expertise

Overview of the Botta’s Research Group

Molecular Modeling

Organic Synthesis

Design and Synthesis of Hit Compounds “Hit to Lead” Optimization Theoretical Study on Target Proteins ADMET properties …

Virtual Screening Pharmacophore modeling Molecular Dynamics ADMET prediction …

Microwave-assisted Click-chemistry Natural compounds synthesis Combinatorial chemistry …

Analytical Chemistry & Toxicology

ADMET properties Membrane permeation Drug metabolism (liver) …

Main Research Areas

Cancer

HIV/AIDS -Reverse Transcriptase -Integrase -ENTRY -NCp7

Tuberculosis -Zmp1 -PtpB

-pyrazoles -pyrazolopyrimidin-7-ones

Kinetoplastid diseases -T. cruzi Tryp.Reductase

-L. infantum Tryp.Reductase -T. cruzi G6PDH -T. cruzi CYP51

Fungal/bacterial infections -macrocyclic amidoguanidines -linear guanidines

Leukemia Neuroblastoma

Medulloblastoma ……..

Infectious disorders

EU Projects involvement

TRIoH Targeting Replication and Integration of HIV- 6th Framework

Programme LSHB CT-2003-503480, from 01/2004 to 06/2007;

ExCellENT-HIT Exploiting Cellular Transport of Nuclear Transcripts as HIV

Innovative Therapy LSHP-CT-2006-037257 11/2006-10/2008;

THINC Targeting hiv integration co-factors, targeting cellular proteins during

nuclear import or integration of hiv

7th Framework Programme-HEALTH-2007-2.3.2-1 from 03/2008 to 02/2012;

CHAARM Combined Highly Active Anti-retroviral Microbicides –

7th Framework Programme 242135 from 01/2010 to 01/2015;

FLUCURE (HEALTH.2010.2.3.3-4 Novel therapeutics against influenza.

FP7-INFLUENZA-2010), Project reference: 259972

from 01/2010 to 01/2014

Design of MSAAs. Research Training Network (HPRN-CT-2000-

00018) “Design and Synthesis of Novel Paclitaxel (Taxol®) Mimics

Using a Common Pharmacophore Model for Microtubule-Stabilizing

Agents (MSAAs)” 09/2000 – 08/2004

COST Action Involvment

CM0602 – Inhibitors of Angiogenesis: Design, Synthesis and

Biological Exploration (ANGIOKEM).

CM0801 – New Drugs for Neglected Diseases

CM0804 – Chemical Biology with Natural Products.

CM1106 – Chemical Approaches to Targeting Drug Resistance in

Cancer Stem Cells.

CM1307 – Targeted Chemoterapy Towards Disease caused by

endoparasites.

FP7-HEALTH-2013

Proposal full title: Imaging technologies for detection, diagnosis and therapy of neuroblastoma Proposal acronym: ImagTechNB Work programme topics addressed: HEALTH.2013.1.2-1: Development of imaging technologies for therapeutic interventions in rare diseases Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Writing collaborator: Dr. Giorgio Maccari Proposal full title: Targeting Kinetoplastid Diseases Proposal acronym: TarKinD Work programme topics addressed: HEALTH.2013.2.3.4-2: Drug development for neglected parasitic diseases Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Writing collaborator: Dr. Francesca Moraca Proposal full title: Targeting the HIV-1 Nucleocapsid Protein to Fight Antiretroviral Drug Resistance Proposal acronym: THINPAD Work programme topics addressed: HEALTH.2013.2.3.1-1: Drugs and vaccines for infections that have developed or are at risk of developing significant anti-microbial resistance Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Writing collaborator: Dr. Mattia Mori

STAGE 1

Proposal full title: Imaging technologies for detection, diagnosis and therapy of neuroblastoma Proposal acronym: ImagTechNB Work programme topics addressed: HEALTH.2013.1.2-1: Development of imaging technologies for therapeutic interventions in rare diseases Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Writing collaborator: Dr. Giorgio Maccari Proposal full title: Targeting Kinetoplastid Diseases Proposal acronym: TarKinD Work programme topics addressed: HEALTH.2013.2.3.4-2: Drug development for neglected parasitic diseases Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Writing collaborator: Dr. Francesca Moraca Proposal full title: Targeting the HIV-1 Nucleocapsid Protein to Fight Antiretroviral Drug Resistance Proposal acronym: THINPAD Work programme topics addressed: HEALTH.2013.2.3.1-1: Drugs and vaccines for infections that have developed or are at risk of developing significant anti-microbial resistance Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Writing collaborator: Dr. Mattia Mori

STAGE 2

Proposal full title: Imaging technologies for detection, diagnosis and therapy of neuroblastoma Proposal acronym: ImagTechNB Work programme topics addressed: HEALTH.2013.1.2-1: Development of imaging technologies for therapeutic interventions in rare diseases Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Proposal full title: Targeting Kinetoplastid Diseases Proposal acronym: TarKinD Work programme topics addressed: HEALTH.2013.2.3.4-2: Drug development for neglected parasitic diseases Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Writing collaborator: Dr. Francesca Moraca Proposal full title: Targeting the HIV-1 Nucleocapsid Protein to Fight Antiretroviral Drug Resistance Proposal acronym: THINPAD Work programme topics addressed: HEALTH.2013.2.3.1-1: Drugs and vaccines for infections that have developed or are at risk of developing significant anti-microbial resistance Coordinator: Università degli Studi di Siena (Prof. Maurizio Botta) Writing collaborator: Dr. Mattia Mori

Targeting the HIV-1 Nucleocapsid Protein to fight

Antiretroviral Drug Resistance

THINPAD website is online http://www.thinpad.unisi.it/index.html

THINPAD Partners

8th IRNCS – Barcelona 2011 9th IRNPAS – Montreal 2013

SMEs in THINPAD

-IRBM Science Park (http://www.irbm.it/) -ViroStatics (http://www.virostatics.com/)

• Active collaborations with SMEs, even before THINPAD

HIV

Cancer

Other disease

• SMEs participated to writing and editing the THINPAD proposal

• The THINPAD Business Plan has been elaborated by SMEs and

discussed with other THINPAD parties

THINPAD Budget – SMEs oriented

Academic partner Academic partner Academic partner

SME partner SME partner

INNOVATION-2 SMEs shall request

> 50% of total budget

THINPAD Management & Decision Making Structure

THINPAD WPs Overview

THINPAD Coordination

Research activity WP2 to WP6

Two coordination workpackages strictly connected with research workpackages

THINPAD Research Work Plan – Step1: LEAD SELECTION

THINPAD Research Work Plan – Step2: preclinical studies

THINPAD Business Plan - highlights

• completion of “first-in-man” enabling studies

• Phase 1 Clinical study

• manufacturing, commercialization

• marketing rights

Out-licensing to Pharmaceutical

Companies

[starting from the end of 2017]

Managed by THINPAD SMEs

[1-2 years starting from the end of the project

(August 2016)]

Step 1 Step2

The Objective is to secure THINPAD NCIs a co-

development/license deal by 2018

the economic potential of the project

in house - SMEs Outlicensing to big Pharma