'Investigar, educar, dialogar. Las lecciones que aprendimos de José Mariano Gago (1948-2015)'. Con este título celebramos los días 1 y 2 de junio de 2016 en la Fundación Ramón Areces un simposio para homenajear la trayectoria de quien fue ministro de Ciencia y Tecnología (1995-2002) y ministro de Ciencia, Tecnología y Educación Superior (2005-2011) de Portugal. Gago desempeñó una labor crucial en el diseño de los planes de desarrollo de la ciencia, la tecnología y la innovación, no solo en su país sino en toda Europa.

1. Spanish National Cancer Research Centre (CNIO)
Going beyond
“excellence”

2. A bit of history…
 The Spanish National Cancer Research Centre (CNIO) was conceived by the
Spanish Government at the end of the 90’s as a part of a long term Strategic Plan to
endow Spain with a series of excellence research centres (CNIO, CNIC, etc)
 CNIO is managed by a Public Foundation currently belonging to the Spanish
Ministry of Economy and Competitivity (MINECO)
 The CNIO has independence to manage its funds and human resources under a
criterium of scientific excellence (External Scientific Advisory Board)
 CNIO personnel enjoys work contracts identical to those of the employees
of private companies
 CNIO has control of its budget, including funds provided by the Ministry
 The CNIO Director reports directly to the Board of Trustees, presided by
the Secretary of State for Research, currently Ms. Carmen Vela
 Main features of CNIO’s administrative system include:

3. CNIO External Advisory Board (2016)
Mariann Bienz (Chair)
Medical Research Council, Cambridge, UK
Joan Massagué
Memorial Sloan Kettering Cancer Center, New York, USA
Angela Nieto
Instituto de Neurociencias, Alicante, Spain
Lauri Altoonen
Biomedicum, Univ. of Helsinski, Finland
Genevieve Almouzni
Institute Curie, Paris, France
Sara Courtneidge
Oregon Health & Science University, Portland, USA
John Diffley
CRUK London Research Institute, Hertfordshire, UK
Denise Galloway
Fred Hutchinson Cancer Research Center, Seattle, USA
Scott Lowe
Memorial Sloan Kettering Cancer Center, New York, USA
Janet Thornton
European Bioinformatics Institute, Hinxton, UK
Michael Bishop
Hooper Research Foundation, San Francisco, USA
Ada Jonah
Weizmann Institute of Science, Rehovot, Israel
José Costa
Yale Comprehensive Cancer Center, New Haven, USA
Karen Vousden
The Beatson Institute for Cancer Research, Glasgow, UK
Alfred Wittinghofer
Max Plank Institute for Molecular Physiology, Dortmund, Germany
Josep Tabernero
Director Oncology Institute, Vall d’Hebron Hospital, Barcelona, Spain

4. 14% non-spanish
Group Leaders Staff Scientists
Lab techs
22% non-spanish
11% non-spanish
Post-doctorals
PhD students
49% non-spanish
41% non-spanish
International Environment

5. Italy
Germany
Portugal
USA
France
Austria
Serbia
UK
Poland
Greece
Romania
Mexico
Ireland
India
Cuba
Croatia
Venezuela
Ukraine
Turkey
Switzerland
Sweden
Slovenia
Russia
ebanon
Israel
Hungary
Colombia
Ciprus
China
Czech Republic
Bulgaria
Argentina
International research environment (countries)

6. Research Organization (2016)
Basic Research
Cancer Cell Biology
4 Research Groups: 2 senior + 3 junior
Molecular Oncology
10 Research Groups: 7 senior + 3 new Junior Groups in 2016
Structural Biology and Biocomputing
3 Research Groups: 1 senior + 2 junior
3 Support Units + 1 new Unit on Text Mining in 2016
E. WAGNER
M. SERRANO
A. VALENCIA
(Vice-Director)

7. Translational Research
Human Cancer Genetics
4 Research Groups: 4 senior
2 Support Units
Clinical Research (CNIO-Hospitals)
3 Clinical Research Units: 1 senior + 2 junior
2 Support Units
2 new CNIO-H12O Clinical Research Units in 2015
Biotechnology
8 Support Units
Experimental Therapeutics
2 sections (Biology & Chemistry)
2 Eli-Lilly labs
Technology Transfer
J. BENITEZ
M. HIDALGO
(Vice-Director hasta Dec 2015)
O. FERNANDEZ-CAPETILLO
(Vice-Director
Director de Innovación)
F. PELAEZ
J. PASTOR
Research Organization II (2016)
A. SANZ

8. CNIO Excellence
(rankings, papers, etc)
Spanish National Cancer Research Centre (CNIO)

9. Total number of publications
0
50
100
150
200
250
300
Totalnumberofscientificpublications
Senior author from CNIO
CNIO co-authorship

10. 0
10
20
30
40
50
60
70
Totalnumberofhighqualitypublications
Impact factor >15
Impact factor 10-15
Excellence: “top papers”

11. International Ranking 2015 (cancer centers)
(out of 4840 institutions (99 Spain) Scimago July 2010-2015)
Excellence with Leadership
CNIO Position in the International Ranking Cancer Centers
Rank Cancer Research Centers Country Ewl
%Ewl: Excelence with Leadership: The amount (in %) of an institution’s scientific
output that is included into the set of the 10% of the most cited papers in their
respective scientific fields in which the institution is the main contributor. This is a size-
independent indicator.

12. Parameter Q1
International Ranking 2015 (cancer centers)
(out of 4840 institutions (99 Spain) Scimago July 2010-2015)
CNIO Position in the International Ranking Cancer Centers
Rank Cancer Research Centers Country Q1
Q1: High Quality Publications: Ratio of publications that an institution publishes in
the most influential scholarly journals of the world, those ranked in the first quartile
(25%) in their categories as ordered by SCImago Journal Rank (SJRII) indicator. This
is a size-independent indicator.

13. Scientific productivity according to Nature Index
AC: Total number of papers from June 1st,
2014, to May 31st, 2015
FC: Fractional count (considering the % of
CNIO authors and number of institutions in
each paper)
WFC: Weighted fractional count in which
some fields of physics is down weighted
Nature Index tracks data from the
publications issued in a selection of
68 high quality journals compiled
by the Nature Publishing Group in
collaboration with Digital Science

14. Ranking of Spanish institutions according to Nature Index
The table includes top Spanish institutions in the field of life sciences, ranked by their FC

15. Spanish Healthcare Institutions Nature Index

16. Associated Hospitals
Oncologists on board
Spanish National Cancer Research Centre (CNIO)

17. Red de Ensayos Clínicos CNIO 2015
Clinical Trial Network
(collaborations ad hoc)
Associated Clinical Units
# Hospital HM - Hospital de Madrid (since 2008)
# Hospital Fuenlabrada (since 2009)
# Hospital Ramón y Cajal (since 2012)
# Hospital La Paz (since 2012)
# Fundación Jiménez Díaz (since 2012)
# Hospital Niño Jesús (since 2013)
# Hosp. Regional y Virgen de la Victoria Málaga (since 2014)
# Hospital 12 de Octubre (since 2015)
# Hospital Clínico San Carlos (since 2015)
# Hospital Quirón (since 2016)
M. HIDALGO
Programme Director CNIO
M.A. QUINTELA
(CNIO)
D. OLMOS
(CNIO)
L. MORENO
(CNIO)
J. MARTÍNEZ
(CNIO-H12O)
L. PAZ-ARES
(CNIO-H12O)

18. Personalized cancer treatment platform
Human tumour
implant in mice
(xenograft)
‘AVATAR’ mice
Bioinformatic
Analysis
Data handling
& integration
Testing
of candidate
drugs in Avatar mice
Therapeutic decision
(personalised treatment)
Datacollection
# Molecular data # Clinical data
# Biological data # Pharmacol. data
# Epidemiologic data # Databases & Publ.
Extraction of clinically
‘useful’ information

19. Hidalgo et al, Can Dis 2014
Avatars recapitulate the patient´s tumor

20. NGS: next generation sequencing
positive:
genetic
councelling
negative:
more research
candidates for
NGS
new genes
We discover new familial cancer genes

21. We read all exome
Rapid translation of results

22. CNIO-Innovation:
Drug discovery,
partnering, lisencing…
Spanish National Cancer Research Centre (CNIO)

23. Drug development at CNIO
Joaquin Pastor, Director of Experimental Therapeutics Program at CNIO

24. Drug discovery at CNIO: Our mission
“Our mission is to serve as a bridge between basic research and
potential therapeutic applications through the discovery and
development of innovative drug candidates for clinical development”

25. VIB: Model for External Collaborations
Currently under
CNIO Internal
development
Drug discovery at CNIO: Our pipeline

26. Development of ATR inhibitors
IN COLLABORATION WITH EXPERIMENTAL THERAPEUTICS PROGRAM
O. F-CAPETILLO

27. 10 Gy + ATRi mM
ATMp
Chk1p
TOLEDO ET AL NSMB (2011)
Clinical Trials 2016
2013
ETP CNIO
Development of ATR inhibitors
Income millestones 2013-
2015:
900.000 euros
Next millestone:
1.500.000 euros

28. 4 Spanish Centers are registered…
“ETP-CNIO” is Unique in Spanish Public Research
Institutions meeting the criteria of “pharma”/academic
experience, integrated capabilities and a proven record of
achievements in academic drug discovery.
Drug discovery at CNIO: part of a network

29. Income from partnering
 2015: Significant increase ( 2 X ) in the number of industrial collaborators (from 10 to 20) .
(new agreements wit Boehringer Ingelheim, Merck KaaG, Daiichi Sankyo…)
Significant increase in funding for fundamental research projects ( preclinical research)
 4.5 M. € secured for collaborative research
Significant increase in funding for fundamental research projects ( preclinical )
1.425773
1.706681
2.675406
2.535579
4.715486
4.48672988
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
2010 2011 2012 2013 2014 2015 (Dic)
Millions
Collaborative Research with partnering

30. Roche: Expanding Innovation Networks

31. CNIO Royalties – commercialization -
 CNIO Intelectual Property Portfolio
 60 patents (2007-2015)
 14 (23%) have been licenced
 In 2015, 1 new priority patent application (ETP)
 24 commertial reagents (antibodies & chemical compounds)
 2014 commertialization
 25 technologies in exploitation: 24 marketed; 1 (ATRi) in development
 Net royalty (2014): 780.840 €
 Income from royalties contributes to the sostenability of the centre, to
support research in the research groups that generate the invention and to
recognize the Inventors.
Spin Offs
Chemical Matter
Biological Material

32. CNIO Inventors (>10% of CNIO personnel)
 CNIO is commited to recognize its Inventors, thorugh a royalty distribution policy
 More than 40 scientist have contributed to the development of the commertialized
technologies. (aprox. 10% of CNIO personnel).
 CNIO Inventors belong to all scientific programs. Molecular Oncology, Biotechnology
and Experimental Therapeutic being the main contributors.
1
2
3
Inventors
Research Groups
CNIO Institution
Inventors per Scientific
Programme Royalty Distribution

33. Training researches in management and bussines administration
In collaboration with IE business School
 23 CNIO scientist have followed
the training
 Building skills & attitudes, Expanding
CNIO Network.
Fostering Innovation Culture

34. Update training &
conferences
PhDs, postdocs, seminars,
meetings….
Spanish National Cancer Research Centre (CNIO)

35. Dean´s Office

36. Training Programs (2014-2015)
PhD Fellowships associated to Severo Ochoa Program
“La Caixa” – Severo Ochoa International PhD Program
Posdoctoral Program for scientists from UK or USA
(Banco Santander Foundation)
Training Program on Molecular Pathology for medical residents
Training Program on Familial Cancer for MIR, BIR and FIR
CNIO Onco-MIR Rotation Program for MIR residents (Celgene)
CNInnOtrain Program IE Business School (Banco Santander
Foundation)
Laboratory Training Program for Undergraduate and
Postgraduate Students
Training Program for Vocational Students (Laboratory
Technicians)
Master in Therapeutical Targets, Research and Development
(Alcalá de Henares University)
Diploma on Translational Research applied to Personalized
Oncology.
Master in Clinical Research Applied to Oncology
(San Pablo-CEU University)
Master in Molecular Oncology (Centro de Estudios Biosanitarios)
Postgraduate Program in Biochemistry, Molecular Biology,
Biomedicine and Biotechnology (Autónoma University of Madrid)
Program for visiting scientists at CNIO (Jesus Serra Foundation)

37. Distinguished Seminars by Oncology Leaders

38. Distinguished Seminars with the French Embassy
Shahragim Tajbakhsh
Instituto Pasteur
7 Noviembre 2014
Jean-Pierre Changeux
Instituto Pasteur
Paris, France
4 Noviembre 2014
Emmanuel Barillot Instituto Curie 13 Junio 2014

39. We organize international conferences
 CNIO Frontiers Meetings (2-3 year)
 Nature-CNIO Symposia (2007, 2010, 2013)
 Co-organizing with International Associations (p.ej. ESO)

40. 2016
Canceromatics III: Tumour heterogeneity
Organizers:
Fatima Al-Shahrour (CNIO, Madrid)
Núria Malats (CNIO, Madrid)
Alfonso Valencia (CNIO, Madrid)
Chris Sander (MSKCC,USA)
Proposed date: 13-16 Nov, 27-30
2017
Molecular Chaperones in Cancer
Organizers:
Nabil Djouder (CNIO, Madrid)
Wilhelm Krek (ETH, Zurich)
Paul Workman (ICR, London)
Helena Yang (Cancer Cell Editor)
Date: 2-4 May
Malignancies in the Central Nervous System: Unknown Biologies towards Therapeutic Applications
Organizers:
Manuel Valiente (CNIO, Madrid)
Massimo Squatrito (CNIO, Madrid)
Richard Gilbertson (Cancer Research UK Cambridge Centre)
Lisa Hutchinson(Nature Reviews Clinical Oncology Editor)
Date: 19-21 Oct
CNIO Frontiers Meetings 2016 and 2017

41. Patrick Sung
Yale University School of Medicine, USA
(Chromosome Dynamics Group)
Chaitanya R. Divgi
Columbia University, NY Presbyterian Hospital, USA
(Seve-Ballesteros Foundation Brain Tumour Group )
Marcin Nowotny
International Institute of Molecular and Cell Biology, Poland
(Structural Bases of Genome Integrity Group )
Sabaticals “Jesús Serra” 2015

42. New logo Women in Science @ CNIO Office

43. Seminars of the Women in Science (WISE) office
2016
María Teresa Fernández de la Vega. President Fundación Mujeres por
Africa, Madrid, Spain
Edurne Pasaban. Mountaineer, Tolosa, Spain
In Her Own Voice: MIT's Earliest Women Scientists. Margery Resnick.
Massachusetts Institute of Technology, Cambridge, US and International
Institute in Madrid, Spain
Woman and Technology: a positive story. María Concepción Ferreras. You
Tube, Head of Partnerships, Southern Europe and Russia
2015
Women in Business and Science : two parallel paths. Natalia González-
Valdés. Corporate Communications and CSR (Corporate Social
Responsibility) Director of L'Oreal Spain
Women at the top: Making it happen. María del Mar Martínez. Director at
McKinsey's Madrid Office, Spain
My life with phage ø29. Margarita Salas Falgueras. CBMSO, Madrid, Spain
A professional career with a gender perspective. Maria Carmen Vela Olmo.
Secretariat of State of Research, Development and Innovation, Ministry of
Economy and Competitiveness, Madrid, Spain
Sex, Science and Society: a triangle that matters? Flora de Pablo. CSIC,
Madrid, Spain
10/05
08/03
19/01
12/01
24/11
09/06
14/04
10/03
17/02

44. Communication & outreach:
News papers, TV, social networks…
Spanish National Cancer Research Centre (CNIO)

45. Communication
CNIO appearances in printed & digital media
(up to 30th November 2015)
0
500
1000
1500
2000
2500
3000
Jan-Mar Apr-Jun Jul-Sep Oct-Dec Total
89 118 87 98
392
98
250 220 193
761
195
378 342
438
1353
387
547
603
760
2297
587 629
685
624
2525
2011
2012
2013
2014
2015 (up to 30 Nov)

46. International presence of CNIO press releases
(from March 2012 to 30th November 2015)
Press Releases Published: 110
Total visits: 308,514
Communication
Average/PR: 2,805
Average/month: 6,855
Top 15 Press Releases

47. Communication
TV and radio broadcasts
[Colombia]

48. Communication
Highlighted appearances in printed & digital media

49. Communication
CNIO news released in front pages

50. Public engagement - Events
Science’s Week
Initiative organised by Madri+d. The attendants learned
more about the CNIO facilities, enjoyed a guided tour in
some of the laboratories and talked with our researchers
about the scientific career and the work In the Centre.
Attendants: 50 people
European Researchers’ Night
Activity organised by Madri+d. Children and adults had
the opportunity to learn more on the CNIO cancer
research. They also extracted DNA from a tomato and
took part in a ‘speed dating’ session with the 40 young
researchers who participated in the activity.
Attendants: 200 people
25/09/2015
05/11/2015

51. www.cnio.es
Engaging society

52. Launched in February 2015 for the initiative “CNIO
Friends”
Communication
From February 15, 2015, to May 12, 2016:
31,026 followers
Reach: 50,767.231 users *
239,664 ‘likes’
16,676 comments
66,555 shares
* Number of people who received contents from the page
Interaction: 73% *
* Number of interactions per followers

53. Internet Day Award – Best Facebook Page 2016
Communication

54. Shown and aired in:CNIO Friends appearances:
Print and digital media: 87
Radio: 18
TV: 13
Video “Become a Friend of CNIO”
Total views in Youtube: 22,844
Video by Amparo Garrido

55. 0 €
10.000 €
20.000 €
30.000 €
40.000 €
50.000 €
60.000 €
70.000 €
80.000 €
90.000 €
100.000 €
2011 2012 2013 2104 2015 2016
Donations CNIO Friends
Donations before the launch
of CNIO Friends
Evolution of donations at CNIO
*
* The initiative “CNIO Friends” was launched in November 2014
(until May 23)

56. CNIO Friends (May 23, 2016): 657 donors
598
8 Sponsors
Benefactors
Friends
51

57. Amigos del CNIO: primera empresa Patrocinadora

58. New CNIO Friends
+
Research on children’s
cancers
Recreational areas in hospitals for
children with cancer

59. • ERC Bridge: An endowment based on the legacy from D. Miguel Martín (ca.
400,000€) to support the Groups of Excellence of the CNIO
 Other legacies can be added in the future
• Goal: to provide financial support to Groups in the the
process of renewing their ERC Grants.
• Eligibility criteria: Groups holding an ERC Grant (Starting, Consolidator or
Advanced), which apply again but do not get the new one right after
• Procedure:
 Groups will place a request to CNIO for this support, indicating the amount
requested and intended destination of the funds
 Maximum amount granted: 100,000€ for Senior Groups; 50,000€ for Junior
Groups
 Maximum time: 1 year
o The amount would be reduced proportionally if the renewal of the grant is
obtained before the end of this 1-year period.
Creation of the “ERC Bridge Endowment”

60. “Constantes y Vitales”: La Sexta + Fundación AXA
 >6,000 participants; 650,000 Km
 100,000 euros to fund the research of the
Microenvironment and Metastasis Group (Héctor Peinado)
at CNIO
 Challenge: to turn Kms into one year of cancer research

61. 0 €
50.000 €
100.000 €
150.000 €
200.000 €
250.000 €
300.000 €
350.000 €
400.000 €
2011 2012 2013 2104 2015 2016
Donations before the launch of
CNIO Friends
Donations CNIO Friends
ATRESMEDIA
Legacies
Evolution of donations at CNIO
*
(until May 23)
* The initiative “CNIO Friends” was launched in November 2014

62. CNIO Friends Fund
CNIO FRIENDS
POSTDOCTORAL FELLOWSHIPS
Duration: 2 years
Starting 2016

63. Our view of the CNIO
Research
Innovation
Solutions
$
Training
Communication
Phylantropy
$
Education
WIS
E
WIS
E
Dean´s
Offic
e
CNI
O
Personnel
Unions

64. Negotiation of the Collective Agreement
Excerpt of the Agreement signed by the
Fundación CNIO Carlos III with the
Works Council on December 20, 2013:
“…..it is agreed to initiate the
negotiations on the 1st of February of
2014 to ellaborate a Collective
Agreement for all the workers of the
Centre”.
Negotiating Table
Activities 2014
- A first draft of the Collective Agreement is elaborated for
discussion
Activities 2015
- January 21: kick off of the negotiation and discussions on
the draft
- July 27: after 18 meetings between the parties, a first
agreed version is reached that is communicated to all the
employees
- Sept-Nov: last changes are incorporated to present a final
version to the meeting of the Board of Trustees in
December
Agreements already reached
- June 23: The Board of Trustees approves
the application of the new timetable based
on 37.5 hours per week in an unbroken day
schedule (Art. 24)
- July 24: The application of the new policy
on the compensation of extra hours beyond
the regular time schedule is approved (Art.
25)
- October 28: The Comisión Delegada
approves the consideration of the 24th and
31st of December as non-working days
(Art. 27)
Director
Managing Director
Dir. Biotechnology
Programme
Dir. Experimental
Therapeutics Prog.
Dir. Administration and
Finances
Dir. Personnel
Chair of the Works Council
5 members representing the
different sections of the
Council:
2 members of CCOO
2 members of UGT
1 member of “Integrando
CNIO”
On behalf of the CNIO On behalf of the Works Council

65. Our view of the CNIO
Research
Innovation
Solutions
$
WIS
E
WIS
E
Dean´s
Offic
e
CNI
O
Personnel
Unions
Training
Communication
Phylantropy
$
Education

66. Spanish National Cancer Research Centre (CNIO)
After substantial operative deficit during (2009-2012),CNIO
accounts are now balanced:
2012: -4.849.000 €
2013: +1.016.000 €
2014: +488.000 €
2015: +100.000 €
2016: aprox. +100.000 € (estimation)
We are, however, returning the ETP loans (2009-2011) to
the Government (~4 M € per year) and this represents a
stress to our savings

67. Looking ahead:
CNIO 2015-2018
Spanish National Cancer Research Centre (CNIO)

68. Spanish National Cancer Research Centre (CNIO)
Groups 2015-2018
Five Junior Groups (Pérez-Moreno, Djouder, Quintela,
Ramón-Maiques, and Lietha) will finish their 5+3 stay at the
CNIO.
Two Junior Groups (Squatrito and Olmos) will have their 5-
year evaluation for a 3-extension at CNIO).
Three new Junior Groups (Peinado, Valiente, Efeyan) would
be at their mid-term period at CNIO.
Recruitment of new Groups (Structural Biology; Immune
System; Microbiota…others?).

69. Spanish National Cancer Research Centre (CNIO)
Challenges
Renew the Severo Ochoa Excellence Acreditation (2016-
2020) (1 million €).
Increase public funding (Government + Competitive).
Increase contracts with Industry (ETP + Groups).
Increase institutional and individual phylantropy.
Recover flexibility: hiring, salaries (productivity)….

70. Highlighted appearances in printed & digital media
Communication

71. Communication
Social media
Launched in June 2009
70 videos
172 subscribers
Total views: 35,963

73. 10 Gy + ATRi mM
ATMp
Chk1p
Development of ATR inhibitors
TOLEDO ET AL NSMB (2011)
Sent to > 70
laboratories
around the world
We provided the
Synthesis
protocol as Supp
Information
Towards the Clinic
TOLEDO ET AL NAT STRUCT MOL BIOL (2008)
2013
ETP CNIO
Income 2013-2015:
900.000 euros

74. CNIO-Merck license agreement

75. Carbo/PEM
+
Demcizumab
Ph1b
FL-NSCLC
(IIIB/ IV)
• Carbo: AUC 6 Q3W x 6
• PEM: 500 mg/m2 Q3W x 6
• DEM: 2.5, 5mg/kg Q3W
and 7.5mg/kg Q3W x4
Demcizumab: inhibidor de Notch en NSCLC fase 1

76. Demcizumab: First-Line NSCLC Study
RECIST Waterfall Plot
Partial Response
9/28 (39%)
Stable Disease
1/28 (48%)
Progress Dis.
3/28 (13%)

77. Collaborations with Big Pharma (Roche)
3 projects funded (2013-
2015)
A total of 520.000 euros

78. H12O-CNIO Clinical Research Units since 2015
Joaquín Martínez Luís Paz-Ares

79. Tumor
detection by
PET/CT
15 days
after detection
No treatment
Mouse with a lung tumor
Untreated mouse
Mouse with a lung tumor
Treated with Notch inhibitor
Tumor
detection by
PET/CT
15 days
After treatment
Accelerate translation from basic research to patients
Notch: A new target for lung and pancreas cancer
Clinical Trial with anti-Notch in pancreas
And lung cancer (ONCOMED Anti-DLL4)
Maraver et al. Cancer Cell, 2012
Manuel Serrano
Tumor Suppression Group
CNIO

80. Pre-treatment
(03/27/2012)
Post-treatment
(04/27/2012)
Anti-DDL4
(Oncomed
Clinical Trial)
Anti-DDL4
?
Discovery of new drug combinations

81. 0 10 20 30 40
0
200
400
600
800
1000
1200
1400
Control mAb
Gemcitabine (30 mg/kg)
Gem (10 mg/kg) +Abrx (30 mg/kg)
Anti-DLL4 + Gem
Anti-DLL4 + Gem/Abrx
Days Post Treatment
TumorVolume,mm3
• Patient progressed on treatment, day 11 (anti-DLL4, 2.5 mg/kg q4w + gemcitabine)
• Patient derived tumor shows increased sensitivity to gem/Abraxane vs. gem alone
• Combination activity observed with anti-DLL4 + gem/Abraxane, but not with anti-DLL4 +
gem
0 10 20 30 40
0
100
200
300
Gem (10 mg/kg) +Abrx (30 mg/kg)
Anti-DLL4 + Gem/Abrx
Anti-DLL4/VEGF + Gem/Abrx
Days Post Treatment
TumorVolume,mm3Gem/Abraxane vs. Gem/Abrx + Anti-DLL4; P = 0.04
Discovery of new drug combinations

82. -100
-90
-80
-70
-60
-50
-40
-30
-20
-10
0
10
Gemcitabine-NabPTX-Dencizumab
Discovery of new drug combinations (pancreas)