Chapter 3 Strategy

3. Strategy (including the strategic process)

Start of Amsterdam Neuroscience (2016-2018)

When Amsterdam Neuroscience began in 2016, there was a solid balance between basic neuroscience and clinical research. The idea behind this strategy was that basic neuroscience provides a deep understanding of molecular and cellular mechanisms, the neuronal systems involved and disease-associated pathology. Using an integrative approach, new insights in neuroscience can find the basis in, or may be linked to, research using complex trait genetics and structural or functional brain imaging. In parallel, we prioritized clinical research, intending to answer burning clinical questions. We identified ‘translational medicine’, a developing research field that fosters the integration of basic research and patientoriented research, as the potential stronghold of Amsterdam Neuroscience.

This implied that Amsterdam Neuroscience aimed explicitly at transforming the fundamental understanding of the biology of the brain into effective health measures. With this aim in mind, we stimulated collaborative research between the science faculties of both universities of Amsterdam UMC, and of external stakeholders from the biotech and pharma industries. Our goal at the time was to accelerate early detection and discovery of disease mechanisms, the identification of novel (drug) targets for intervention and paving the way towards drugs discovery and novel Advanced Therapy Medicinal Product (ATMP) interventions, all in clinical trials.

Figure 1 Infographic of the research organization of Amsterdam Neuroscience in the period 2016-2018.

At the time, Amsterdam Neuroscience introduced an IAO team of business developers. The purpose of the team is to facilitate this research strategy by initiating, supporting and structuring the scientific discussions leading towards the project definition and execution of Translational Neuroscience and clinically oriented contracts, which are sponsored by external stakeholders from the biotech and pharma industries in the fields of Translational Neuroscience, neurology and psychiatry.

Organization of research (2016-2018)

Amsterdam Neuroscience started with nine research programs (see Figure 1). Five of these research programs focused on specific brain and nervous system diseases, and four programs focused on innovation and technology. The programs were organized in a matrix in order to underscore the fact that innovation takes place at all levels of study: from molecular to cellular studies, to circuitry and intact brain and behavior, both at the individual as well as population level.

Strengths

Translational Neuroscience & Medicine Ambitious (young) Principal Investigator Community Largest Neuroscience community in The Netherlands Strong links with biotech & pharma-industry

Lateralisation in Amsterdam ADORE Investment opportunities in ADORE Clinical trial opportunities via IAO Better patient stratification Translation medicine infrastructure Lack of leadership in some Research Programs Principal Investigators lacking internal drive to reach out beyond borders of their own labs or institutes Lack of cohesive strategy within and between Research Programs

Opportunities Weaknesses

Threats

Diversification of focus and attention of Principal Investigators Lack of funding for high end core facilities such as biocomputation & bioinformatics Lack of dedicated research time for young MD, PhDs

Figure 2 Infographic summarizing the SWOT (Strengths, Weaknesses, Opportunities & Threats) highlights of Amsterdam Neuroscience. The analysis is based on the institute’s 2016-2018 metrics and the trend-watching by Amsterdam Neuroscience’s management team in communication with the program leaders. The nine research programs had dedicated steering committees and included, on average, 25 Principal Investigators and additional talent. Shared infrastructure and translational efforts were being realized. Graduate training and the involvement of medical residents in research were implemented with the aim of guiding the younger generations through an integrative approach within each of the research programs.

Midterm evaluation

Halfway into the six years of our accreditation period as an institute (i.e., in 2019, for the period 2016-2018) we performed an internal inspection of the research organization with the help of an independent ad hoc scientific advisory committee. While we were able to reflect on many strengths, opportunities and weaknesses, we also saw a trend of three major threats (see Figure 2). First, the conditional grant system in the Netherlands and Europe had become increasingly competitive and reflected a worldwide trend that led to a diversification of the attention span of our investigators. Second, the central administration of Amsterdam UMC needed to make confirmative and positive decisions towards (central funding of) core facilities required for top-line research. Third, there appeared to be a structural lack of dedicated research time allocated to young MD-PhD investigators and team leaders.

Restructuring the organization in 2019

As part of the internal SWOT analysis at the beginning of 2019 by the directors and the management team of Amsterdam Neuroscience (see Figure 2, p. 10), we made changes in the positioning and focus of two of the nine research programs. First, the former Neurotechnology program was changed into a new Systems and Network Neuroscience program. Secondly, the former Brain Mechanisms program was changed into a new Cellular and Molecular Mechanisms program. While the collaboration within the former Neurotechnology domain was fruitful, it turned out to be primarily strategic. Further internal discussions and development of insights had meanwhile led to the realization that a wider perspective on the higher dimensional levels of brain organization is needed in the coming years.

What’s more, the former Brain Mechanisms program in essence had too large a core group of founders working on very different – but interconnected – levels, from molecular and cellular mechanisms up to neural networks and systems. Hence to create a better balance, a select number of co-workers from the former Brain Mechanisms program were regrouped under the newly established Systems and Network Neuroscience program together with the founding group of former Neurotechnology investigators, while a second subgroup of the former Brain Mechanism program regrouped under the new Cellular and Molecular Mechanisms program.

Figure 3 Infographic of the research organization of Amsterdam Neuroscience in the period 2019-2021.

In line with this internal SWOT analysis, the infographic of Amsterdam Neuroscience’s strategy was changed accordingly (please compare Figure 1 (p. 09) and Figure 3 to appreciate how this affects the organization). In addition, separate SWOT analyses of the research programs are attached to this report to provide further rationale on these changes. The program leaders of the restructured organization (see Appendix 1, p. 33) have performed a SWOT analysis based on the perspective of the past three years of the research programs’ existences (2019-2021) and given their vision on the future up to 2024 (see Appendix 2, p. 37).

2016

2017

2018

2019

Odile vd Heuvel Camiel Boon

Rob de Bie Charlotte Teunissen Claudi Bockting

Joep Killestein Helmut Kessels Christiaan Lohmann Ysbrand vd Werf Guido van Wingen Karin Verweij

2020

2021

Hilgo Bruining Yolande Pijnenburg Martijn vd Heuvel

Christiaan Vinkers Nicole Wolf

2022

Matthijs Brouwer Ronald v Kesteren Ingo Willuhn Leon de Bruin

Figure 4 New appointments of full professorships in various departments in line with the research program strategy of Amsterdam Neuroscience over the period 2016-2022.

New leadership in 2019: research program leaders and full professorships

At the same time as restructuring the organization, we also appointed new program leaders in seven out of the nine research programs. Individual program leader appointments were made for Cellular & Molecular Mechanisms (CMM), Complex Trait Genetics (CTG), Neuroinfection & -inflammation (NII), Compulsivity, Impulsivity & Attention (CIA) and Mood, Anxiety, Psychosis, Stress & Sleep (MAPSS), while two new program leaders (and task force members) were appointed for both Systems & Network Neuroscience (SNN) and Neurovascular Disorders (NDIS). Leadership for Neurodegeneration (ND) and Brain Imaging (BI) has been firmly in place since 2016 but may need revision in 2022-2023. Furthermore, a total of sixteen new full professorship appointments were achieved between 2016 and 2021 in line with Amsterdam Neuroscience’s overall research program strategy, and an additional lineup of four similarly-positioned appointments will be made in 2022 (see Figure 4).

Health funds

Central government

Neurologists

Companies

Expertise centers

Neuro scientists

Psychologists Media

Psychiatrists

Patients

Investors Students Politics

Staff Supporters care, research & education

Regional government

Science Parks

Figure 5 From 2019 onwards, Amsterdam Neuroscience has been aiming for a more widespread community of stakeholders. In addition to addressing the question of how to organize the external stakeholder network and how to organize patient recruitment for clinical trials (i.e., Hersenonderzoek.nl), we have also been strategically positioning the teams of investigators at international level (such as in ENIGMA, the Human Brain Project and the SynGO consortium). Furthermore, we have been firmly addressing our (social) media strategy and focusing on involving complementary fields of research (through the Amsterdam Research Board and the Amsterdam Valorisation Board).

The strategy of the institute (2019-2021)

In the fall of 2019 Amsterdam Neuroscience adopted the slogan: ‘Connecting the people, the science and the brain.’ To direct Amsterdam Neuroscience’s activities during the second half of its accreditation period, it was decided the institute should focus on the following seven major strategic points of attention for the years 2019-2021 with regards to investments, activities and efforts from the research institute and its directors in order to bring the new strategy in line with its campaign to reach a wider community of stakeholders (see Figure 5, p. 12).

I. More emphasis on the establishment of infrastructure by means of key funding (in addition to alliance & PoC funding).

Over €80 million (Vrije Universiteit Amsterdam) funding was secured to build a new research center housing the research facilities of the Center for Neurogenomics and Cognitive Research (CNCR) at the

Vrije Universiteit Amsterdam and over €160 million (Amsterdam UMC and ADORE) funding was secured to build an innovative research and diagnostics center for ADORE (Amsterdam Oncology and Neuroscience

Research). This will include a new IPS center facility, an integrated proteomics and genomics center, a total body PET facility and a biocomputation and bioinformatics center. II. Organize webinars: bring more cohesion across the Amsterdam

Neuroscience community and support the branding of Amsterdam

Neuroscience.

We have been organizing webinars more than ever. In the fall of 2020, Amsterdam Neuroscience and Amsterdam UMC teams joined forces and organized the online Amsterdam UMC & COVID-19 research event. It featured an interview with Dr. Anthony Fauci and several young clinical residents who are busy in the fight against

COVID-19. We had more than 1,000 active attendants and another 10,000 participants who streamed the content later on. In addition to this, the Amsterdam Neuroscience Annual Meeting 2020 was also completely online (with 500 active attendants). And the 2021 edition of the Annual Meeting consisted of a hybrid event (with 200 visitors on-site and 400 online). Moreover, all Translational Neuroscience

Network (TN2) events were online webinars, currently visited by around 100 participants per webinar each month. III. Work on staff recruitment: more emphasis on how they fit in the strategy of Amsterdam Neuroscience.

See Figure 4 (p. 12) for new appointments made to date. IV. Protected research time for Principal Investigators and staff is an important and sine que non condition for translational research.

Key opinion leaders of Amsterdam UMC joined a national initiative around Recognition & Rewards – Room for Everyone’s Talent and directors have been reiterating this issue with heads of departments since 2019. Many heads of departments respond positively to this request but prefer tailormade career planning via shared decision-making rather than through formalized top-down rules. V. Work on national funding programs.

There were major efforts made by current directors and program leaders in initiating national funding opportunities.

These include Brainscapes, ABOARD, Brainmodel (see use cases in Appendix 6, p. 83), in addition to MedTech, Biotech Booster,

Knowledge Transfer Organization-NL and more. VI. Work on risk mitigation.

Leadership needs to have a strategy in place to respond to possible scenarios of successful Principal Investigators being offered a tempting position elsewhere. This is currently done by the proper embedding and awarding of new initiatives both at the level of personalized funding for excellent Principal Investigators (for instance through ERC funding) as well as by awarding (large) team science (as is becoming very evident in so-called large scale (inter) national consortia funding. VII. Increase Amsterdam Neuroscience’s PR relations, branding and identity.

There was major and new professional support for this part of our strategy. We published annual magazines, produced professional video material, sent out monthly newsletters, and posted more than 200 news items on a renewed research website, around 500 tweets and >200 LinkedIn posts. We are currently receiving more than 20,000 views every month (see use cases in Appendix 6, p. 83).

B i o m a r ke r s Clinical trial phase I & ATMPs D rug screening

Clinical trial phase II

assaysCellular animals PoC in

& valid ati on Identifi cati o n ADME/Tox Pharmacology (partnering) mechanisms Disease

Clinical trial phase III

Industry Alliance Office - IXA

The Industry Alliance Office is a one-stop-shop for biotech and pharma industry, for fast contracting of basic and translational neuroscience and clinical trials.

Figure 6 The essence of how the IAO is positioned as a business development organization of Amsterdam Neuroscience. For more information, see the Industry Alliance Office website. The IAO team support both Translational Neuroscience contract research and clinical trials. For a quick overview, see the IAO introduction video.

Facilitating valorization through the concept of an Industry Alliance Office

Translational Neuroscience is at the core of the collaboration between university labs, clinical practice and the biotech and pharma industries In Amsterdam Neuroscience this is facilitated and supported by an embedded business development office – the so-called ‘Industry Alliance Office’ (IAO) – to bridge the gap between academia, medical faculty, hospitals and the biotech and pharma industries. The IAO acts on behalf of the entire Amsterdam Neuroscience organization and is a full-service shop (from scouting to contracting) for the biotech and pharma industries for basic and Translational Neuroscience, but also for clinical trials up to Phase III. Since 2013 the IAO has turned parts of scientific excellence into commercial value, research assets, access to patient cohorts and material, and infrastructure based on a disease-orientated approach. In 2018 we upscaled this embedded business development activity to include the entire Amsterdam Neuroscience area, including location AMC and, in 2022, the UvA. The essence of how the IAO is positioned in the organization of Amsterdam UMC is illustrated in Figure 6. Cumulative categories of contracts and deal flow are illustrated in Figures 7 (p. 15) and 8 (p. 16), respectively.

Contracting Values (€k) of Amsterdam Neuroscience | Industry Alliance Office

14,000

12,000

10,000

8,000

6,000

4,000

2,000

0

@C@ ;A;>; ;A9B< CONTRACTS - Location DBL ;A@<> 9A::>

CONTRACTS - Location MBD

2013 2014 2015 2016 2017 2018 2019 2020 2021

Year

Figure 7 Cumulative contracting value of IAO-initiated research at Amsterdam Neuroscience (pooled for Amsterdam UMC, location De Boelelaan – DBL and the Neuroscience department of the Vrije Universiteit Amsterdam in green; Amsterdam UMC location Meibergdreef – MBD in orange. More dissemination of the IAO strategy for the Neuroscience department of the UvA is aimed for the coming years). The figure shows an increasing trend over the years 2013 to 2021, reaching a substantial value of €57.2 million, as part of the institute’s valorization strategy.

Figure 8 Deal flow through the years at Amsterdam UMC, location De Boelelaan pooled with the Neuroscience department of the Vrije Universiteit Amsterdam for preclinical, translational and clinical research and trials contracted via the IAO under supervision of the directors of Amsterdam Neuroscience. Left: contract research categorized per disease area (AD: Alzheimer’s Disease, FTD: Frontotemporal Disorders, PD: Parkinson’s Disease, MS: Multiple Sclerosis, Psych: Psychiatry). Right: distribution of the different domains of contract research (preclinical, translational and clinical research and trials). The relative contribution of the three domains varies through the years. An equal contribution from each domain is the ideal goal.