U N I V E R S I T Y O F C O P E N H A G E N

F A C U L T Y O F H E A L T H A N D M E D I C A L S C I E N C E S

B R I D G E - T R A N S L A T I O N A L E X C E L L E N C E P R O G R A M M E

P R O J E C T S Y N O P S I S T E M P L A T E1

Project title Maintaining sinus rhythm by SK channel inhibition

Mentor 1 Bo Hjorth Bentzen, Associate Professor, Dept. of Biomedical Sciences, Faculty of

Health and Medical Sciences, University of Copenhagen (bobe@sund.ku.dk)

Mentor 2 Morten Grunnet, Chief Scientific Officer, Acesion Pharma (mgr@acesionpharma.com)

Framework The fellow will work in a well-established high performance collaborative

environment, where great translational research is key for success. Acesion Pharma

(AP) is a Danish biotech company that aims to develop SK channel inhibitors as

treatment of atrial fibrillation (AF). Investors in AP are Novo, Broadview Ventures,

SEED Capital and Wellcome Trust. AP have recently successfully conducted a phase I

clinical trial with a novel SK channel modulator.

Bo Bentzen’s group, which focuses on understanding AF and discovering new

treatments and AP are heavily involved in translational research, and have many

international collaborators and experiences with academic mentorship also from

being a partners in the EU horizon 2020 PhD training network (AFib TrainNet).

The collaboration between the mentors is well established and fruitful, and the fellow

will work with both academic and industrial scientists, which will allow for a unique

mentorship in solid translational research and preclinical drug discovery.

Project

synopsis

Atrial fibrillation is the most common cardiac arrhythmia affecting 2% of the total

population. Current treatment of atrial fibrillation (AF) often relies on controlling the

heart rate. An alternative is to convert the chaotic fibrillation of the atria to sinus

rhythm. However, current anti-arrhythmic drugs are hampered by poor safety and/or

efficacy. Based on preclinical work SK channel inhibition appears to constitute an

attractive alternative. With this project we would like to establish new porcine

1 The CV’s and project synopsis of each mentor team will be posted on the programme webpage in advance of the

admissions process to the programme.

PAGE 2 OF 2 models of arrhythmia and investigate possible cardiac benefits of maintaining sinus

rhythm using SK channel modulators.

Profile of

potential

fellow

Keen interest in drug discovery Desire to work in the cross-field between industry and academia Experience with cardiovascular physiology Experience and interest in working with animal models of cardiac disease

U N I V E R S I T Y O F C O P E N H A G E N

F A C U L T Y O F H E A L T H A N D M E D I C A L S C I E N C E S

B R I D G E - T R A N S L A T I O N A L E X C E L L E N C E P R O G R A M M E

M E N T O R C V T E M P L A T E1

Name Bo Hjorth Bentzen

Title PhD

Current

department(s)

Dept. of Biomedical Sciences, Faculty of Health and Medical Sciences, University

of Copenhagen

Current position(s) Associate Professor (tenured), Research group leader

Education/training Education: 2015: Harvard Business School, Pasteur Program (leading and managing innovation) 2010: Ph.D. Health Sciences, University of Copenhagen 2006: M.Sc. Human Biology, University of Copenhagen

Training and work experience: 2014 –2018 Director of joint project between University of Copenhagen and Acesion Pharma, funded by Innovation Fund Denmark 2014- Associate Professor, Dept. of Biomedical Sciences, UCPH 2012-2015 Manager of in vitro pharmacology, Acesion Pharma, Denmark 2012-2013 Postdoc, Danish National Research Foundation Centre of Cardiac Arrhythmia, Univeristy of Copenhagen 2011–2012 Research Scientist, NSDiscovery, NeuroSearch A/S.

Scientific career

profile

Profile: I am a skilled electrophysiologist and pharmacologist with both academic and pharmaceutical training. I work on diagnosing, understanding and treating cardiac arrhythmia. To this end I take advantage of my knowledge on drug discovery, cell, tissue and animals experiments. I do basic research to understand the physiology of the heart and apply this to explore novel ways of diagnosing and treating cardiac disorders. I have a strong passion for innovation and collaborative projects between industry and academia, and have served as the director of a Grand solution project (Innovation Fund DK) 2014-2018, and I am currently appointed “Innovation Scout” at the department, and former board member of the Industrial PhD and Postdoc Association. My research group, which I started in 2015, currently employees 1 postdoc, 4 PhD-student and 3 shared master students. We are utilizing our expertise in experimental cardiac models and translational science in our collaborative projects. Together with

1 Do not exceed two pages.

The CV’s and project synopsis of each mentor team will be posted on the programme webpage in advance of the

admissions process to the programme

PAGE 2 OF 3 the Niels Bohr Institute we are developing radical new tools for fetal arrhythmia detection, with Acesion Pharma novel treatments of AF, and with the University of Miami and Linköping we are finding new treatments for inherited LQT syndrome. We also have a strong focus on understanding the mechanism of arrhythmia and have joint projects on the role of genetic and epigenetics in AF together with Morten Olesen BMI/RH and Prof Ellinor, Broad Institute of Harvard and MIT. My group spun out from the former Danish National Research Foundation Centre of Cardiac Arrhythmia, and we have a finely established national network of collaborators. Moreover as partners in the EU horizon 2020 PhD training network Afib Trainnet we have also established a broad international network.

Bibliometric

summary

41 peer-reviewed publications, 9 first authorships, 10 second authorships, 6 last

authorships. 3 patent applications and 1 granted patent. H-index: 15; 621 citations.

1) Jensen K, Skarsfeldt MA, Stærkind H, Arnbak J, Balabas MV, Olesen SP, Bentzen BH,

Polzik ES. Sci Rep. 2018 Nov 1;8(1):16218.

2) Skarsfeldt MA, Bomholtz SH, Lundegaard PR, Lopez-Izquierdo A, Tristani-Firouzi M,

Bentzen BH. Acta Physiol (Oxf). 2018 Jul;223(3):e13049

3) Diness JG, Skibsbye L, Simo-Vicens R, dos Santos JL, Lundegaard P, Citerni C, Sauter

DRP, Bomholtz SH, Svendsen JH, Olesen SP, Sørensen US, Jespersen T, Grunnet M,

Bentzen BH. Circ Arrhythm Electrophysiol. 2017 Oct;10(10). pii: e005125

4) Simó-Vicens R, Kirchhoff JE, Dolce B, Jensen LA, Speerschneider T, Sørensen US,

Grunnet M, Diness JG, Bentzen BH. Br J Pharmacol. 2017 Dec;174(23):4396-4408

5) Liin S.I., Larsson J.E., Barro-Soria B., Bentzen BH., Larsson P. Elife 2016 Sep 30;5. pii:

e20272.

6) Skarsfeldt, M.A., Jepps, T.A., Bomholtz, S.H., Abildgaard, L., Sørensen, U.S., Gregers, E.,

Svendsen, J.H., Diness, J.G., Grunnet, M., Schmitt, N., Olesen SP., Bentzen BH. Pflugers

Arch 2016. 468, 643–654

7) Liin, S.I., Silverå Ejneby, M., Barro-Soria, R., Skarsfeldt, M.A., Larsson, J.E., Starck Härlin,

F., Parkkari, T., Bentzen, B.H., Schmitt, N., Larsson, H.P., et al. Proc. Natl. Acad. Sci. U.S.A

2015. 112, 5714–5719.

8) Soltysinska, E., Bentzen, B.H., Barthmes, M., Hattel, H., Thrush, A.B., Harper, M.-E.,

Qvortrup, K., Larsen, F.J., Schiffer, T.A., Losa-Reyna, J., et al. PLoS ONE 2014, 9, e103402

9) Bentzen, B.H., Grunnet, M., Hyveled-Nielsen, L., Sundgreen, C., Lassen, J.B., and

Hansen, H.H. Obesity. 2013; 21, 985–992.

10) Bentzen, B.H., Nardi, A., Calloe, K., Madsen, L.S., Olesen, S.-P., and Grunnet, M. The

small molecule NS11021 is a potent and specific activator of Ca2+-activated big-

conductance K+ channels. Mol. Pharmacol. 2007. 72, 1033–1044.

Contributions to

mentoring,

training,

supervision

I want my mentees to grow and become independent researchers, and help them

find the best path forward no matter if it is in academia or industry. 1 PhD student

from my research group has graduated, and he has pursued an academic career as a

postdoc in the US. Three postdocs have finished in my lab, and currently hold jobs as

scientists in private companies. In addition to pre-graduate teaching i am course

organizer of the BRIDGE course “translational tools I”, and have co-organized 3 PhD

courses: “Ion Channel Symposium”, UCPH. Moreover I lecture in the “Master of

Industrial Drug Development” course at UCPH”

U N I V E R S I T Y O F C O P E N H A G E N

F A C U L T Y O F H E A L T H A N D M E D I C A L S C I E N C E S

B R I D G E - T R A N S L A T I O N A L E X C E L L E N C E P R O G R A M M E

M E N T O R C V T E M P L A T E1

Name Morten Grunnet

Title PhD, Professor

Current

department(s)

Acesion Pharma, Lundbeck A/S and Institute for Drug design and Pharmacology,

University of Copenhagen

Current position(s) Chief Scientific Officer, Acesion Pharma; Director Research and Development and

PA to EVP for R&D, Lundbeck A/S; Professor (honorary) at Institute for Drug

design and Pharmacology, University of Copenhagen

Education/training 2017-: Director Research and Development and PA to EVP for R&D

2014-2017: Head of Department, Synaptic Transmission In Vitro, at Lundbeck

2012-2014: Principal Scientist at Lundbeck A/S

2012-: Professor (honorary) University of Copenhagen

2011: Doctor Degree from Natural Sciences, University of Copenhagen

2011-: CSO, Board member and co-founder Acesion Pharma

2011-2012: Scientific Director and Head of NS Academy, NeuroSearch A/S

2007-2011: Professor at Department of Biomedical Sciences, UCPH

2009-2011: Head of Drug Discovery Portfolio Management, Neurosearch A/S

2005-2009: Head of Department, Cardiac Physiology, NeuroSearch A/S

2004-2005: Research Scientist at NeuroSearch A/S

2002-2007: Assistant professor at Department of Medical Physiology, UCPH

2002-2004: Co-founder and scientist at Poseidon Pharmacuticals

2002: Medical PhD

1998: Master of Science (Biology)

Scientific career

profile

My entire research career has been focused on ion channels in excitable tissue. I

have concomitant with my basic research career and academic career (4 years

served as a full professor, currently Honorary Professor), always had a strong

focus on drug development and worked in both biotech and pharma industry. I

1 Do not exceed two pages.

The CV’s and project synopsis of each mentor team will be posted on the programme webpage in advance of the

admissions process to the programme

PAGE 2 OF 3 have co-founded two biotech companies, and have extensive experience with

drug discovery, translational research, project management and leadership. I

have headed different departments and been member of the discovery

management group as scientific director. My project manager experience cover

everything from early stage discovery to mature full scale projects encompassing

up to 30 project members. In 2011 I co-founded a new biotech company, Acesion

Pharma, where I’m currently CSO and has additionally in 2012 started to work at

Lundbeck A/S. Initially in a specialist role as Principal Scientist, later as Head of

Department for 20 people at Synaptic Transmission In vitro and currently as

Director in Research and Development and personal assistant to the EVP for R&D.

Bibliometric

summary

125 peer review papers, 2 peer review book chapter, 17 patents, > 5000 citations,

H-factor: 38

1) Richards, KL.; Milligan, CJ.; Richardson, RJ.; et al.;Selective; PROCEEDINGS OF THE NATIONAL

ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Volume: 115 Issue: 34 Pages:

E8077-E8085 Published: AUG 21 2018

2) Diness, Jonas Goldin; Skibsbye, Lasse; Simo-Vicens, Rafel; et al.; CIRCULATION-ARRHYTHMIA AND

ELECTROPHYSIOLOGY Volume: 10 Issue: 10 Article Number: e005125 Published: OCT 2017

3) Qi, XY; Diness, JG.; Brundel, BJJ; et al. CIRCULATION Volume: 129 Issue: 4 Pages: 430-440

Published: JAN 28 2014

4) Liang, B; Nissen, JD.; Laursen, M; et al.; CARDIOVASCULAR RESEARCH Volume: 101 Issue: 1

Pages: 175-184 Published: JAN 1 2014

5) Schmitt N; Grunnet M; Olesen, SP; PHYSIOLOGICAL REVIEWS Volume: 94 Issue: 2 Pages: 609-

653 Published: APR 2014

6) Skibsbye, L; Poulet, C; Diness, JG; et al.; CARDIOVASCULAR RESEARCH Volume: 103 Issue: 1

Pages: 156-167 Published: JUL 1 2014

7) Diness, JG.; Skibsbye, L; Jespersen, T; et al. HYPERTENSION Volume: 57 Issue: 6 Pages: 1129-

U195 Published: JUN 2011

8) Diness, Jonas Goldin; Sorensen, Ulrik S.; Nissen, Jakob Dahl; et al.; CIRCULATION-ARRHYTHMIA

AND ELECTROPHYSIOLOGY Volume: 3 Issue: 4 Pages: 380-U121 Published: AUG 2010

9) Yang, Yanzong; Yang, Yiqing; Liang, Bo; et al.; AMERICAN JOURNAL OF HUMAN GENETICS

Volume: 86 Issue: 6 Pages: 872-880: JUN 11 2010

10) Frokjaer-Jensen, C; Davis, M. W; Hopkins, Christopher E.; et al. NATURE GENETICS Volume: 40

Issue: 11 Pages: 1375-1383 Published: NOV 2008

Contributions to

mentoring,

training,

supervision

Include a statement on your mentoring philosophy

I have supervised 13 Master students, 12 PhD students, and mentored several

postdocs. These people now hold jobs in academia as postdocs, assistant and

associate professors or the industry as scientists.

Teaching experience from various undergraduate courses in molecular biology

and cell biology and graduate courses in specific courses about ion channels,

transporters and receptors. Co-organizer of the PhD course “Ion Channel

Symposium”