GENNARO CILIBERTO - Dottorato in Biochimica e Biologia

GENNARO CILIBERTO: PERSONAL DATA
Date of Birth: September 22, 1954
Place of Birth: Napoli
Citizenship: Italian
Status: Married
Home Address: P.le R. Ardigò, 30/A, 00142 Roma
Home Telephone Number: +39 0659606495
Mobile Telephone Number: +39 3356117822
[email protected];
[email protected];
E-mail
Addresses:
[email protected]
Offices:
• Dipartimento di Medicina Sperimentale e Clinica, Campus Germaneto,
Università di Catanzaro Magna Graecia, Viale Europa 88100 Catanzaro
Telephone: + 39 09613694980
Fax: + 39 09613694073
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Direzione Scientifica IRCCS Istituto Nazionale Tumori Senatore “G.Pascale”,
Via Mariano Semmola 80100 Napoli
Telephone: + 39 0815903757
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SHORT PROFESSIONAL PROFILE
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Molecular and Cellular Biologist with expertise in the following areas: control
of gene transcription, signal transduction by cytokines and growth factors,
somatic gene therapy, cancer cell biology and genetics, immunotherapy of
cancer.
More than 25 years of research management experience.
Full Professor of Molecular Biology starting year 1990.
On leave of absence from University from 1991 to 2009, due to employment
at the Merck Sharp and Dohme research center IRBM P. Angeletti in
Pomezia (Rome), resumed Academic activity at the University of Catanzaro
“Magna Graecia” in October 2009.
Past experience at Merck include responsibilities for several early drug
discovery programs (target identification to phase I clinical trials) and
membership of several Merck Research Laboratories (MRL) decision-making
committees.
For 3 years (2006-2009) Site Head and Managing Director IRBM P. Angeletti
in Pomezia, and manager of approximately 200 staff members.
From August 2008- to September 2009 World Wide responsibilities at MRL
for Basic Research efforts in the Oncology.
In Nov 2009 co-founder of a biotechnology company, Takis s.r.l., a spin-off
of the IRBM P. Angeletti, with the main focus on research and development
in Oncology.
In March 2012 appointed Scientific Director of IRCSS Istituto Nazionale
Tumori, Senatore “G. Pascale” Napoli
Member of several national and international scientific societies.
Since 1989 elected member of the European Molecular Biology Organization
(EMBO).
Co-author of more than 200 publications in Peer Reviewed international
journals (total I.F. 1290; H-index = 59). Total citations as of January 10,
2012 = 12.774 (Source: ISI Web of Science). Average citations/paper = 48
Large experience in Technology transfer as witnessed by Co-inventorship in
25 international granted patents/patent applications
Reviewer and editorial board member of several international journals and
editor of textbook for graduate students.
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EDUCATION
2nd Medical School, University of Naples 1978 M.D. : 110/110 with honors
ACADEMIC APPOINTMENTS
Scientific Director of IRCCS Istituto Nazionale Tumori, “Senatore G.
Pascale” Napoli, Italy, start date March 1st 2012
Full Professor of Molecular Biology, Faculty of Medicine, University of
Catanzaro "Magna Graecia", 1995 to present
Full professor of Molecular Biology, Faculty of Pharmacy, University of
Naples (Italy) 1990-1994
Associate Professor of Genetics at the University of Pisa (Italy) 1987-1990
Visiting Scientist at the E.M.B.L., Heidelberg, Germany 1987 Jan-Oct
C.N.R. (Italian National Council of Research) staff scientist at the "Center
of Experimental Oncology and Endocrinology", now IEOS, Naples. 19831987
Staff Member Scientist at the E.M.B.L., Heidelberg 1982-1985
Post-doctoral fellow at the European Molecular Biology Laboratory
(E.M.B.L.), Heidelberg 1979-1982
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PAST PHARMA & BIOTEC MANAGERIAL EXPERIENCE
TAKIS s.r.l. – Nov 2009-Jan 2012
Title: President
In November 2009 G. Ciliberto co-founded Takis s.r.l., a spin off of I.R.B.M. P.
Angeletti, located in Castel Romano (Rome). Takis’ mission is the development
of innovative cancer therapies using as core technologies in vivo nucleic acid
delivery with viral vectors and gene-electro-transfer. www.takis-it.it
Key Accomplishments
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Takis is currently hiring five employees, is involved in two cancer
vaccine programs slated to start early clinical development and
has established several external research and collaboration
agreements with biotechs, pharma companies and universities.
I.R.B.M. P. Angeletti, MRL Laboratories – July 2006 to Sep 2009
Title: Vice President Merck Research Laboratories, Site Head of IRBM and
Amminstratore Delegato of IRBM SpA.
Manager of a group of approx. 200 researchers involved in Lead Identification
and Lead Optimization efforts in the areas of Oncology, Antiviral and Metabolic
Disorders
Key Accomplishments
• Under his 3 years supervision IRBM contributed to the MRL
development pipeline with 10 preclinical drug candidates,
approved by the internal Merck Research Laboratories Pre-clinical
Development Research Committee (PDRC), some of which now
under advanced clinical development
MRL Laboratories - July 2008 to Sep 2009
Title: Oncology World Wide Basic Research Head (WWBRH)
Member of Oncology Franchise Research and Strategy Committees and Manager
of Oncology Research groups located in 4 distinct research sites
Key Accomplishments
• Co-ordinated consolidation and prioritization of Oncology Basic
Research activities in two research sites in line with the
implementation of a new global Operating strategy. Supervised
approval to pre-clinical development by the internal Merck
Research Laboratories Pre-clinical Development Research
Committee (PDRC) of all oncology programs originated at 4
research centers.
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Molecular and Cellular Biology Dept. at I.R.B.M., Oct 2000 – July 2006
Title: Senior Director 2000-2002, Executive Director 2002-2006
Initially Manager of a group of 30 Scientists involved in the development of new
gene-delivery platforms for the genetic cure of diseases (gene therapy)
Subsequently Manager of a group of 50 Scientists involved in Oncology, Peptide
Therapeutics and Antiviral Research.
Key Accomplishments
• Creation of novel Adenoviral vectors for Gene Delivery
• Advanced in vivo Gene Electro Transfer Tecnology to Non Human
Primates
• Developed drug-controlled in vivo gene expression systems
• Established an innovative platform technology for
Cancer
Vaccines and coordination of two programs advanced for clinical
development
• Coordinated Merck Oncology in-licensing efforts for Cancer
Vaccines and Monoclonal antobodies that led to the establishment
of several external partnerships with the following companies:
Pierre Fabre, Agensys, Geron, Inovio and Idera.
• Supervised the creation at IRBM of the Therapeutic Peptide
Center of Excellence
Genetics Dept. at the Istituto Ricerche di Biologia Molecolare (IRBM P.
Angeletti) Pomezia, Roma (Italy) 1991-2000
Title: Program Coordinator 1991-1999, Senior Director, 1999-2000
Manager of a group of 20 Scientists involved in drug-discovery of biologics
mimetics or antagonists of IL-6 family cytokines
Key Accomplishments
• Generation of Interleukin-6 superantagonists
• Generation of Interleukin-6 superagonists
• Generation of CNTF variants with novel pharmaceutical
properties for the treatment of obesity
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MEMBERSHIPS
Società Italiana di Biofisica e Biologia Molecolare (In Feb 2011 elected
Member of the Board)
Società Immunologia e Immunologia Clinica (SIIC)
EMBO Member (elected in 1989)
Member of the Association New York Academy of Sciences
iSBTc International Society for Biological Therapy of Cancer
NIBIT - Network Italiano per la Bioterapia dei Tumori
Board Member of Fondazione Chiara D'Onofrio
Board Member of BIOGEM s.c.a r.l. Scientific Committee
EDITORIAL EXPERIENCE
Past Member of Editorial Boards for EMBO Journal, EMBO Reports and
Cell Death and Development
Editor of the Book: “Cytokine Inhibitors”: edited by Ciliberto, G. and Savino, R.
(2001) Marcel Dekker, Inc. - New York
Coauthor of the Textbook "Argomenti di Biologia Molecolare": G. Ciliberto and G.
Melino, Seu Editor, Rome 2006
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RECENT INVITED PRESENTATIONS
February 2012
Ordine dei medici della provinciamdi Salerno, February 11
Conferenza: Pillole di aggiornamento: geni-tumori-ambiente: ricerca, diagnosi,
terapia
Titolo dell’intervento: Farmacogenetica e terapia genica
October 2011
University of Napoli, Department of Molecular Pathology, October 13
Seminar Title: A new platform technology for therapeutic cancer vaccines
October 2011
Viral Oncology Research, 3rd International Meeting, Napoli Oct 4-6, 2011
Title: DNA-electroporation based cancer vaccines
September 2011
Conference on Gene Vaccination in Cancer, Ascoli Piceno September 15-17, 2011
Title: Combining antigen engineering and heterologous prime-boost genetechnology as a strategy for the optimization of therapeutic cancer vaccines
June 2011
Transgene, Strasbourg, June 15
Title: Anti-HER3 monoclonal antibodies
November 2011
Sigma-Tau Industrie riunite,
Title: A new platform technology for Cancer Vaccines
July 2011
Molecular Biotechnology Center, Univ of Torino, July 12
Seminar Title: A novel genetic platform for Cancer Vaccines
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SCIENTIFIC INTERESTS AND COORDINATION OF PROJECTS
Cancer Stem cells and Biological Therapy
At the end of his permanence at IRBM in year 2009 G. Ciliberto started efforts towards
the study of cancer stem cells and some surface receptors that are emerging as
potential new targets for therapy of cancer. Part of these efforts are presently being
continued by G. Ciliberto as an Academic investigator of the University of Catanzaro
Magna Graecia.
In particular Prof. Ciliberto is currently involved in two projects: a) the first, in
collaboration with University of Rome “La Sapienza”, Department of Molecular Biology
and Medicine is the directed to the establishment and characterization of a biobank of
Lung cancers from malignant pleural effusions; b) the second is focussing on the study
of monoclonal antibodies directed against one surface receptor of the ErbB family,
namely ErbB3/HER3 which seems to be involved in mechanisms of resistance to EGFR
and HER2 inhibitors.
These efforts have so far yielded 7 publications from 2009 until July 2011. An
additional manuscript has been submitted recently.
Therapeutic Cancer Vaccines
In year 2001 G. Ciliberto started at IRBM a new program entirely dedicated to Cancer
Immunotherapy and focussed on the development of Therapeutic Cancer Vaccines.
The program capitalized on the previous expertise matured by Ciliberto and his
collaborators about in vivo somatic Gene Therapy program.
The group initially defined a solid platform technology capable of inducing strong and
durable immune responses towards self-tumor associated antigens (TAAs). This very
innovative platform consists in the sequential use of Adenoviral vectors and DNA
electro-gene-transfer in heterologous prime-boost sequence. This technology was
complemented by a variety of additional approaches aiming at improving TAA
immunogenicity, such as generation of fusion proteins with immunoenhancing moieties
and optimization of codon-usage.
Finally the group focussed on a subset of well defined tumor antigens here listed: EpCAM, CEA, ErbB2, Telomerase and MMP11. Generated prototype Cancer Vaccines
against them, and demonstrated their efficacy in mouse tumor model.
A subset of these vaccines were chosen by Merck as pre-clinical candidates and
advanced into clinical development. In year 2010 a subset of these programs has been
transferred by Merck to Takis through a licensing agreement.
The program started in 2001 and gave rise to a wealth of publications (no 29) and
patent applications (no 8).
G. Ciliberto as Department Head acted as overall Program coordinator supervising
several group leaders involved in distinct activities.
Somatic Gene Therapy
In year 1996 G. Ciliberto as Head of the Genetics Department at IRBM started a large
effort in somatic gene therapy. The program was aiming primarily to the establishment
of a solid platform for stable, efficient and non-immunogenic gene delivery. In this
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respect the project was divided into three arms: a) generation of novel Helperdependent adenoviral vectors; b) generation of hybrid viral vectors such as Ad/AAV
vectors, and c) direct delivery of naked plasmid DNA into skeletal muscle via electrogene-transfer. Furthermore additional efforts were directed to the generation and
optimization of ligand-dependent transcriptional regulatory switches that could allow
stringent control of gene expression.
Significant progress was achieved in all sublines of this project as witnesses by a long
record of publications (a total of 30) and patents (no 7). G. Ciliberto as Department
Head acted as overall Program coordinator supervising several group leaders involved
in distinct activities.
Several somatic gene therapy vectors were advanced into pre-clinical testing in a
variety of animal models of anemia, viral hepatitis and finally also cancer, in rodent as
well as non human primate models, achieving significant proof-of-concept results in
stable disease correction as well as tight temporal control of gene expression.
The program started in 1996 and ended in 2001.
Structure-function of IL6 and other gp130 cytokines
At the end of year 1990 G. Ciliberto moved to IRBM initially with the role of Program
Coordinator, subsequently as Head of the Genetics Department.
His scientific interests were mainly directed to the study of IL-6 and of other cytokines
which use GP130 as common signalling receptor (IL-11, Oncostatin M, CNTF).
The main focus of his research was the generation of cytokine variants with modified
pharmacological properties that could be used for therapeutic purposes. In this respect
the principal target was IL-6. Thanks to the combination of molecular modelling, sitedirected mutagenesis, immunoprecipitation and in vivo/in vitro assays these efforts led
to the generation and functional characterization of IL-6 variants defined as superantagonists and also as super-agonists.
A parallel effort of his group was directed to the definition of the role of the same
cytokines in disease. In other words significant efforts were directed to validate IL-6 as
a target for therapy, using a variety of animal models, mainly KO and transgenic.
The entire program led to the publication of a total of 76 papers and 10 patents. The
program started in 1991 and ended in year 1999. However, several papers were still
published in years following y1999 due to many collaborations with outside groups
using animal models, mainly IL-6 KO derived in Ciliberto’s lab.
Trancriptional control of acute phase response
In year 1986 G. Ciliberto became an independent investigator and established a
research group at the “Dipartimento di Biochimica e Biotecnologie Mediche” of the
University of Napoli “Federico II”.
The project started in 1986 and ended in 1991 when G. Ciliberto moved to IRBM P.
Angeletti. The project dealt with the identification of molecular mechanisms at the
basis of the transcriptional control of acute phase response genes in liver. The main,
albeit not exclusive, focus was given to the study of the regulation of the prototypical
acute phase response gene in humans, C-reactive protein. That study led to start my
interests in the cytokine Inteleukin-6, which was identified as a main inducer of IL-6
transcription in the liver. The entire effort led to the publication of 23 papers, 18 of
them with G. Ciliberto as first or last author.
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TRANSLATIONAL RESEARCH EXPERTISE
Most of the research activity conducted by Prof Gennaro Ciliberto from year 1991 to
2009 when he was an IRBM P. Angeletti/Merck employee has been inspired to
translational principles. Indeed the mission of a Pharmaceutical Company such as
Merck, of which IRBM P. Angeletti was a subsidiary, is to conceive and develop new
therapies for diseases with high unmet medical need.
Given the various roles as Manager covered by G. Ciliberto at IRBM P. Angeletti, his
job profile required to become an expert in translational science.
The three main programs G. Ciliberto sequentially coordinated in those years, namely
a) IL-6 cytokines superantagonists and superagonists
b) Somatic Gene Therapy
c) Therapeutic Cancer Vaccines
were all directed to the generation and optimization of new drug candidates.
Furthermore, these efforts required a strong Intellectual Property protection for all
these discoveries. This was achieved through filing a significant number of
International Patents, in order to generate a rich Patent Portfolio. Indeed the net result
of this effort was the generation of 3 distinct sets of Patents totalling a number of 25,
the first one for the protection of Cytokine Variants with modified pharmacological
properties (no 10), a second for Somatic Gene Therapy vectors (no 7); the last for
Therapeutic Cancer Vaccines (no 8).
G. Ciliberto has, therefore, acquired significant expertise in the process of identification
of patentable discoveries and in the intellectual property protection of relevant
findings.
In particular, the Therapeutic Vaccine Program led to the definition of two therapeutic
cancer vaccines clinical candidates which were advanced to Phase I/II clinical trials.
The first (V930/V932) was directed to co-target simultaneously two Tumor Associated
Antigens (CEA and HER2) and was the subject of a multicentric clinical trial involving
USA and Italian clinical sites. The results of that trial will be the object of a publication
in preparation.
The second vaccine (V934/V935) was directed against the universal tumor antigen
telomerase.
The cancer vaccine program at Merck was entirely conducted for all pre-clinical aspects
by G. Ciliberto’s group at IRBM. When the vaccine candidates were approved internally
at Merck for clinical development a Development Team was assembled between IRBM
and Merck investigators at other Merck sites, called Cancer Vaccine EDT (Early
Development Team), which was chaired by G. Ciliberto for some years (2004-2006)
until he stepped down when he became IRBM P. Angeletti Site Head.
Both vaccines were partnered with the American Company Inovio V934/V935 was
partnered also with the American Company Geron
Finally, as Oncology Franchise WWBRH at Merck and as IRBM Site Head, G. Ciliberto
supervised several other programs (in Oncology, HepC and obesity), which were
advanced to clinical development under his management.
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COORDINATION OF INTERNATIONAL PROGRAMS
During the time G. Ciliberto was an employee of IRBM P. Angeletti, he participated to
the global Oncology efforts of Merck Research Laboratories.
At the time the Oncology activities were located at five research sites:
USA: West Point (Pennsylvania), Boston (Massachusetts), Seattle (Washington)
Japan: Banju research center in Tsukuba
Italy: IRBM P. Angeletti in Pomezia.
The overall Coordination of all Oncology was under the Direction of a Franchise Head,
initially Dr. Stephen Friend, subsequently Dr. Gary Gilliland, both distinguished
American Scientists, very well known in the Oncology Field.
Reporting to the Franchise Head was the World Wide Basic Research Head (WWBRH),
with the role of coordinating all Basis Research Activities, which included
a) identification of new Oncology Targets
b) validation of these Targets
c) prioritization of Targets for Drug Discovery
d) generation of Therapeutic Leads against these targets and their optimization
e) in licensing efforts
f) approval of new compounds for further clinical development, by an internal
Merck Committee
g) interface with the Clinical Oncology Group at Merck for trial design.
G. Ciliberto in years 2004-2008 was the IRBM Site Lead for Oncology, interacting
directly with the Franchise Head. During the last year, 2008-2009, he was appointed
WWBRH (World Wide Basic Research Head). This activity involved participation to
coordinating Committees, frequent travels to the US sites and interactions with several
scientists at various research sites.
G. Ciliberto’s contribution to the Merck Oncology pipeline, as listed in the attached
certificate was rich and consisted in the following drug candidates that were selected
for further clinical development by a Merck Internal Committee. For reasons of
confidentiality the identity of each candidate cannot be disclosed, but just the type.
Some of these drug candidates, each one being the result of the effort of dedicated
research groups, are in advanced (Phase II/III) clinical development by Merck.
MK-3336, MK-4827, MK-2512, MK-4101, MK-5710:
MK-1968: immunomodulator
MK-0646: monoclonal antibody
V930/V932, V934/V935: cancer vaccines
small molecule inhibitors
Among the documents presented is a Merck Statement by the present Franchise Head
Prof. G. Gilliland which summarizes Prof. Ciliberto’s roles and contributions for the
Merck Oncology network by the current Merck Franchise Head.
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ORGANIZATION OF COMPLEX FACILITIES
From year 2006 untill September 2009 Prof. G. Ciliberto has been Amministratore
Delegato of IRBM P. Angeletti and as Vice President of Merck Research Laboratories in
Italy he was the Site Head (Direttore Scientifico) of IRBM P. Angeletti.
In this role he administered a budget of approximately 30 M €/year and a Staff Group
of approximately 200 employees.
In this role he was responsible for investments in new assets and assisted in the
coordination and maintenance of several scientific and technical capabilities the IRBM
site.
The following features need particular mention:
1) Creation in year 2007 of a Fully Robotized Biotechnology Facility for the
automated growth expansion, collection and processing of cell lines which was
called Robolab. This was equipped with the following instruments: 2 SelecT, 1
Cello, 1 Beckman workstation ORCA.
2) Creation in years 2006-2007 of a Fully Equipped Peptide Center of Excellence
for the Small and Large Scele Synthesis and purification of Peptides, which was
at the time the reference Peptide Center Of Excellence at merck
3) In year 2008 achievement of International AAALAC accreditation for the Animal
Facility
4) Fully robotized Biotesting Laboratory for High Throughput screening of chemical
compounds in biological assays
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RECENT RESEARCH GRANTS OBTAINED
2011
PRIN 2009
Title: Monoclonal antibodies directed against the HER3 family member as tools to
inhibit signal transduction from ErbB family members in tumor cells: understanding the
relationships between endocytosis, receptor degradation and cell growth inhibition.
Duration: 2 years. Funding 52.699 €
Institution: Dipartimento di Medicina Sperimentale e Clinica, Univ di Catanzaro
2010
AIRC IG Grant
Title: Targeting HER3 receptors with monoclonal antibodies
Duration: 3 years. Funding 85.000 €/year
Institution: Dipartimento di Medicina Sperimentale e Clinica, Univ di Catanzaro
2007
Fondo Agevolazioni Ricerca MIUR
Title: Vaccini Antitumorali
Institution: IRBM P. Angeletti
2006
MIUR PNR 2005-2007
Title: Sviluppo di Farmaci Biologici Innovativi
Institution: IRBM P. Angeletti
2003
MIUR FIRB 2001
Title: Vaccini ricombinanti per la prevenzione e cura del cancro
Institution: IRBM P. Angeletti
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