2020 Boosting translational medicine in Academia - Spark-BIH

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2020 Boosting translational medicine in Academia - Spark-BIH
2020

Boosting
translational
medicine in
Academia
                BIH
2020 Boosting translational medicine in Academia - Spark-BIH
© SPARK-BIH | Berliner Institut für Gesundheitsforschung, November 2020

                                                                          SPARK-BIH
                                                                          c/o Berlin Institute of Health
                                                                          Anna-Louisa-Karsch-Straße 2
                                                                          10178 Berlin

                                                                          spark@bihealth.de
                                                                          www.spark-bih.de
2020 Boosting translational medicine in Academia - Spark-BIH
SPARK program in Berlin....................................................................................................................................               6

SPARK-BIH in Numbers – SPARK projects from 2015 – 2019............................................................................                                        13

SPARK-BIH Projects – Our newly funded & mentored SPARK Teams of 2019........................................                                                              19

SPARK-BIH Projects – Our SPARK Teams that started funding & mentoring in 2015 - 2018 ............                                                                         29

SPARK-BIH Projects – Mentored-only SPARK Teams ........................................................................................                                   63

SPARK-BIH Projects – Our newly funded & mentored I4H Teams of 2019 ...................................................                                                    67

SPARK-BIH Project Glossar.................................................................................................................................                76

SPARK-BIH Photo Copyrights..............................................................................................................................                  77

SPARK Team ............................................................................................................................................................   78
SPARK program in Berlin
The SPARK program in Berlin was             universities world-wide. The SPARK         embedded within BIH Innovations, the
founded in 2015 by Prof. Dr. Craig Garner   network serves as a resource for           joint technology transfer of BIH and
and Prof. Dr. Ulrich Dirnagl with the       knowledge, advisors and examples           Charité. Thereby, SPARK in Berlin has
support of the Stiftung Charité. The        of best practice. An annual meeting        grown from supporting about 4 projects
goal was and is to support academic         brings together the leadership of all      per year with 50.000€ each to a program
inventors in translating their research     SPARK programs to discuss global           that currently funds and mentors almost
findings into therapies, products and       health challenges, strategies to improve   30 project teams within the validation
services, such as novel therapeutics        translation and how to augment             fund. Employees from Charité, the Max
(small molecules, biologics, cellular       the    SPARK    educational     program.   Delbrück Centre for Molecular Medicine
therapies),   medical     devices    and    An international workshop on Bio           and the BIH can apply with translational
diagnostics for unmet medical needs.        Innovation and Entrepreneurship brings     projects from all medical areas.
                                            together SPARK participants from all
The program in Berlin was modeled           around the globe.                          Projects are selected for funding by
after the successful SPARK program                                                     the validation fund in an annual call
at Stanford University which Prof.          In 2018 the Berlin Institute of Health     for proposals with a panel of external
Dr. Garner was a member of. Since           (BIH) decided to perpetuate the program    experts. Selection criteria include the
its founding in 2006 SPARK has grown        and to include SPARK-BIH as part of        hight of innovation, size of the unmet
to a global network with programs           their mission to support translational     medical need, competitive advantage
implemented at more than 50                 medicine. SPARK-BIH was successfully       over current gold standards, data quality

                                                                4
SPARK Team

and likelihood of translational success.    SPARK educates faculty, students and         and develop initial prototypes of their
Two funding tracks have been                fellows on topics relevant for translation   solutions. These teams are augmented
implemented in the validation fund:         and business development via their           by the addition of team-members from
Earlier projects are supported with up to   educational series including forums and      other disciplines such as business
50.000€ for one year in track 1 whereas     workshops.                                   and design to create truly holistic
later and more mature projects are                                                       solutions. In future it is planned that
supported for two years with a budget       As of 2019, the Inventors for Health         the most promising ideas can apply to
of more than 50.000€ as part of track       Program has been implemented at              be further developed by SPARK-BIH and
2. Funding is strictly milestone-based      SPARK-BIH to serve as the front-end          the validation fund or the Digital Health
and projects are closely monitored by       of innovation and growth for early-          Accelerator.
members of the SPARK team.                  stage ideas. The Inventors for Health
                                            Program has been developed in close
Teams selected for funding by the           cooperation with their partner, the          Dr. Tanja Rosenmund
validation fund enter the SPARK-            Stiftung Charité. The program focuses on     Program Manager & Manager
BIH program. Here, projects are             developing breakthrough ideas in health      Validation
supported with mentoring, advice, and       and is currently made up of 2 phases
an extensive network to accelerate the      – a development and funding phase.
translation of their academic invention     Through a series of hands-on bootcamps,
into a marketable product to the benefit    inventors identify and elaborate on their
of patients and society. Furthermore,       ideas, develop entrepreneurial skills,

                                                                5
SPARK-BIH is part of the global SPARK network
Over 50 different institutions have established or are developing their own versions of the SPARK program. The
mission is to improve human health by uniting academics and industry experts around the globe to generate an
efficient, effective and exciting pathway for translation of academic discoveries and innovative solutions through
education and project support.

                                                        6
SPARK-BIH is part of BIH Innovations
SPARK-BIH and the validation fund are part are part of BIH Innovations, the joint technology transfer office of
the Charité and the BIH. BIH Innovations consists of four parts enabling the translation and commercialization of
academic projects. SPARK-BIH is closely working with the patents & licensing team to in order to protect and exploit
innovations.

       Patents, licensing, law                                                  Strategic cooperations
       and startup consulting                                                   Forming and managing-
       Identifying, protecting                                                  strategic co-operations
       and commercializing                                                      with academia and industry
       assets (with key partner:
       Ascenion)

       Validation Fund/
                                                                                 Digital Labs
       SPARK-BIH
                                                                                 Translating digital health
       Translating medical                                                       solutions to patients/
       inventions (drugs, diag-                                                  market (incl. Digital
       nostics, medtech) into                                                    Health Accelerator)
       products and solutions
       to benefit patients

                                                          7
How do SPARK-BIH and the validation fund work?
SPARK-BIH and the validation fund were created to support academics in translating their inventions into novel
therapeutics, medical devices and diagnostics that address unmet medical needs.

SPARK-BIH and the validation fund are part of BIH
Innovations, the joint technology transfer of BIH and                                              SPARK-BIH provides
Charité.                                                                                           mentoring, funding,
                                                                                                  external expertise and
The purpose of SPARK-BIH and the validation fund is                                                     education.
to support academic projects with funding, mentoring,
                                                                                                                                  Funding
advice and education to accelerate their translation                    Mentoring
                                                                                                                               The BIH validation
for the benefit of patients and society.                             Project managers                                          fund offers strictly
                                                                   support SPARK teams                                          milestone-based
Our support is reflected in translationally relevant              with regular meetings                                     funding since 2018 and
preclinical data, sound clinical trials, new IP, novel life          to identify needs                                         is divided into two
                                                                    and experts, access                                       tracks for different
science startups and industry partnerships as well as             progress and guide the                                     project maturity. Calls
licensing agreements.                                              project development                                           are announced
                                                                                                                                     annually.
By applying for funding within the validation fund
to enhance the translatability of your project you
automatically profit from the SPARK-BIH mentoring and
education program.
Project proposals are evaluated on the basis of several                     Advisor                                        Education
aspects, the most important being: (1) addressing an                     Experts advise
                                                                                                                         Public educational
unmet medical need, (2) the potential for translation into           SPARK teams on topics
                                                                                                                       seminars introduce the
                                                                    such as HTS, medicinal
the clinics.                                                                                                           drug and device devel-
                                                                       chemistry, manu-
                                                                                                                      opment process, discuss
Refunding mechanisms (e.g. shares) secure that in case of           facturing, clinical trials,
                                                                                                                          IP and business
                                                                         regulatory and
                                                                                                                        (entrepreneurship) -
commercial successes a part of the revenues will be used                    business
                                                                                                                           relevant topics
                                                                          development.
for future development programs.

                                                              8
How does SPARK-I4H work?
The Inventors for Health (I4H) Program is a pilot program that has been developed together with the Stiftung
Charité and addresses scientists with very early projects and ideas.

Traditionally, the barriers-to-entry for medical innovation,
research and development have been high. The I4H pilot program
is democratizing that process and allowing for citizens and
patients to co-develop solutions together with scientists and medical
professionals.                                                             Phase I               Phase II
Unlike traditional incubation programs focusing purely on later         I4H Bootcamp            I4H Grant
commercialization, the I4H program focuses on developing
breakthrough medical innovations by developing the people behind
the ideas through skill-building, mindset change, and exposure to a
                                                                           Problem –
network of innovators and medical change-makers.
                                                                            Solution                Funding
Accordingly, the I4H pilot program tests a novel program design.          Exploration
In future it is planned to continue key components of the program
as scouting mechanisms to identify and develop early ideas.
Subsequent funding might be realized by established funding                 Product –
                                                                                                   Prototype
programs such as SPARK-BIH and the validation fund or the Digital            Market
                                                                                                  Refinement
Health Accelerator.                                                        Exploration
Currently, I4H is made up of two phases: In the first phase,
inventors develop their idea(s) rapidly through design-based
approaches, with help from experts from other disciplines. In the           Scale and
                                                                                                      MVP
second phase, funded teams advance their ideas to minimally                Robustness
viable products (MVP) for testing and further development, making
use of SPARK-BIH.

                                                                  9
SPARK-BIH: Maturity Pipeline of funding opportunities by Stiftung Charité
and BIH Validation Fund

                               Support by SPARK-BIH mentoring & education program

                                                                               BIH Validation Fund by

                                                                                                            BIH Validation
                                                                                                            Fund Track 2
                                                                                                            Projects in a more
                                                                                                            mature phase which are
                  I4H Incubator of                                            BIH Validation                typically patented and
                                                                              Fund Track 1                  need further supporting
                                              I4H Grant                       Projects in an early phase    data and additional
                                              Stiftung Charité                of development which are      development. Examples
                                              Outstanding projects            clearly later than pure       are safety, dose-finding,
                  I4H Bootcamp                which took part in phase        research projects. Visible,   medical chemistry,
                  Phase I with interactive    I are selected for fund-        first proof of principle      regulatory strategy,
 PROJECT STATUS

                  Bootcamps for               ing to develop a strong         data which need to be         clinical trial design
                  hands-on skill and          PoC. Selected inventors         validated and completed       and further to be
                  mindset development         will receive up to 50%          and are usually used to       translated into the clinic.
                  with a focus on             salary support and a            file a patent. Funding        Funding above €50,000,
                  entrepreneurial and         maximum of €50.000 in           amount is up to €50.000,      with a funding duration
                  design-lead approaches.     project support.                funding duration is 1 year.   is 2 years.

                                             Maturity & translatability of projects

                                                                         10
SPARK-BIH
             in Numbers

SPARK projects from 2015-2019
                                11
                         11
Number of SPARK projects from 2015-2019

                         12
Translational Success of SPARK projects from 2015-2019
                    of our SPARK teams stated that                                                             of our SPARK Pharma teams were

71%                 the SPARK program was crucial to
                    advance the translational pathway                                      80%                 able to proceed their preclinical
                                                                                                               development program to the next
                    of their project                                                                           stages

                                                                                             100%
                                                                                                            of our SPARK medtech
                    Follow-on applied research funding                                                      and IVD teams were able to
  14                programs were acquired by our
                    SPARK teams amounting to more
                                                                                                            proceed their medical device or
                                                                                             IVD development program to the next stages
                    than 10,5 Mio EUR
                                                                                              All of them also recruited an expert in CE
                                                                                              certification or started with the technical doc-
                                                                                              umentation and /or QMS 13485 establishment

  11       SPARK teams have filed patents
           during or after participation in SPARK
                                                                                              for their product

  3      SPARK teams have an option contract
         or term sheet for potential licensing of
                                                                                               87              Accelerator or Bootcamp programs
                                                                                                               were started by our SPARK teams
         their patent ongoing
                                                                                               1614            Prices or Awards have been won by
                                                                                                               our SPARK teams

    7               SPARK teams have founded or plan
                    to found a startup
                                                                                                87
                                                                                                                of our SPARK teams prepared
                                                                                                                clinical trials for their project or

    8               SPARK teams have had                                                                        were able to continue and improve
                    cooperations with industry                                                     14           the running clinical trials

*All numbers are based on a survey that was submitted by 21 SPARK teams that started funding until 2018 as well as consultation of the patent team of BIH
innovation

                                                                               13
Biomedical Fields and Areas of SPARK funded projects from 2015-2019

                                   14
Statistics on SPARK organized Educational Seminars 2015-2019

 “I am here to get or keep in touch with “entrepreneurial” ideas and find inspiration for translation from science
 to business. It is the first time I participated and very much liked the format.“ – Attendee in Forum in 2017

                  50                                                                            33
                                    SPARK organized                                                               Different topics on
                                    educational seminars                                                          drug & device
                                    from 2015-2019                                                                development

                                                                             Overall satisfaction

                                                        97%*                 with the educational
                                                                             lecture series from
                                                                             2015- 2019

                                                                                                97
                                   Participants in the                                                            Speakers giving a
               >1100               educational lecture                                                            presentation from
                                   series from 2015- 2019                                                         2015 - 2019

*Numbers are based on evaluations submitted by seminar attendees for 79 speakers at 40 different educational seminars in the years 2015-2019

                                                                               15
“In the beginning I considered SPARK just another program among all those university-based
supporting initiatives. I hoped for some financial support but not more. However, it turned
out to provide something much more valuable than money. SPARK provides multi-level
competence, bringing in the right experts at the right time. In our case, this was not only
the critical mind of other SPARKees, but also clinicians, advisors and business experienced
people, pushing our project to a much higher level. Giving us a special pre-hearing during the
Go-Bio application was extremely helpful. The payless support by a team of experts, tailor
made to our needs was a so far unique experience for me. Personally, I learned a lot, starting
from being a purely academic person, I meanwhile got a sense of how business people think
and regulatory boards work. Still there are a lot of things I need to learn to survive in this new
        environment. I highly appreciate to have SPARK on my side on this journey.     “

							Prof. Christoph Schwarzer

                                                16
SPARK-BIH
                  Projects

Our newly funded & mentored SPARK Teams of 2019
                                                  17
“The SPARK program was instrumental
in supporting the MyoPax idea from a basic research project into a solid
  GMP-compatible product presently under preclinical testing. Without
  SPARK, any translational effort into the clinic would have ceased two
                              years ago.“

                                                    Prof. Simone Spuler

                                   18
A novel peptide to regenerate the central nervous system
                        PRINCIPAL INVESTIGATOR:
                        Dr. Sarah-Christin Starossom                Pharma - small molecule
                        Prof. Dr. Friedemann Paul                      Neurology
                        Charité

SUMMARY                                                PROJECT GOALS
The team has identified a novel mechanism with
                                                       • Develop a patentable therapeutic agent
pro-oligodendrogenic and remyelinating capacity.
Based on that mechanism the project aims at            • Test in vitro dose-response
developing a novel therapeutic option for multiple     • Submit invention disclosure
sclerosis. Although myelin and oligodendrocytes

                                                                                                  Track 1
are thought to be the prime target for autoimmune
attacks in multiple sclerosis (MS), there are          LONG-TERM GOALS
currently no FDA approved drugs targeting the
induction of endogenous remyelination and              • Novel drug therapy for Multiple
oligodendrocyte repair. The therapeutic induction of
                                                         sclerosis
oligodendrogenesis and/or remyelination is a highly
unmet need for MS and other diseases of the CNS.       • License to Pharma

                                                  19
Validation of anti-cancer agents in patient-derived canceroids

                      INVESTIGATOR:                                        Pharma - small molecule
                      Prof. Dr. Reinhold Schäfer
                      Charité                                                 Oncology

          SUMMARY                                              PROJECT GOALS
          The project aims to validate modulators of a
                                                               • Validate drug candidates in
          transcription factor as agents against cancer. The
          validation will be conducted in patient-derived        patient-derived canceroids
          canceroids. About 1/3 of all cancers are mutant      • Submit invention disclosure
          RAS-driven and cause up to 1 million deaths each
Track 1

          year. Novel therapies targeting signaling effector   LONG-TERM GOALS
          proteins downstream of RAS are already in clinical
          use, however with uncertain long-term effects. The   • Start an investigator initiated trial
          approach may provide a new avenue for anti-RAS
                                                                 for cancer patients based on
          therapies.
                                                                 repositioned drugs
                                                               • License to Pharma

                                                          20
“SPARK put me on track to focus on the goal to develop a drug and ac-
                quire the competencies needed.“

 “SPARK helped me to put my exploratory, basic scientist mind to the
sideline for a while, to focus on bringing the results of our research to
                          patients and market.“

                                                  Prof. Regine Heilbronn

                                    21
Exploring a novel therapeutic target in cystic fibrosis

                       PRINCIPAL INVESTIGATOR:                                    Pharma - small molecule
                       Dr. Anita Balázs
                       Charité                                                       Pulmonology

          SUMMARY                                                   PROJECT GOALS
          The project aim is to validate and pre-clinically
                                                                    • Validate and pre-clinically test drug
          test candidates previously identified as potential
          modulators of an alternative pathway to circumvent          candidates for CF
          the primary ion transport defect in cystic fibrosis       • Submit invention disclosure
          (CF). CF is a life-limiting disease caused by mutations
Track 1

          in the CFTR gene. Although highly effective CFTR
          modulators are emerging, ~10-15% of patients will         LONG-TERM GOALS
          not benefit from these therapies, while the high price
          of these drugs prevents access in many countries.         • Novel drug therapy for cystic fibrosis
          There is an unmet need to develop alternative
                                                                      and other muco-obstructive lung
          therapy strategies to bypass CFTR dysfunction and to
          restore epithelial ion transport in CF.                     diseases
                                                                    • License to Pharma

                                                               22
A novel solution for a total artificial heart
                        INVESTIGATORS:
                        Dr. Marcus Granegger                        Medtech
                        Tim Bierewirtz                                 Cardiovascular Devices
                        Charité

SUMMARY                                                PROJECT GOALS

                                                       • Build a functional model /
The team aims to develop a functional prototype of
an implantable total artificial heart (TAH) for the      prototype
treatment of end-staged heart failure in pediatric     • Perform in vitro validation
and adult patients. Available TAHs are risk prone      • Submit invention disclosure

                                                                                                    Track 1
regarding reliability, blood damage and thrombus
formation. The novel concept promises superior
                                                       LONG-TERM GOALS
performances by means of reliability, implantability
and hemocompatibilty.
                                                       • Novel cardiologic medical device for
                                                         end-staged heart failure
                                                       • License to medtech or startup foundation

                                                  23
Development of a stapler for solid organs

                       PRINCIPAL INVESTIGATOR:                                   Medtech
                       Dr. Panagiotis Fikatas
                       Charité                                                      Surgery

          SUMMARY                                                   PROJECT GOALS
          The aim of the project is the final development and
                                                                    • Build a functional stapler prototype
          validation of a novel surgical stapler that allows the
          minimal-invasive, wedge-shaped resection of solid         • Perform validation tests in “dry-lab”
          organs. Current solutions for solid organ resection are
          limited and carry the risk for intra- or postoperative    LONG-TERM GOALS
Track 2

          bleeding and are associated with a high probability
          of fistula development. The novel stapler allows          • Startup foundation
          to cut solid organs safely and with reduced risk of       • CE certification as a medical device
          complications.

                                                               24
A novel advanced therapy medicinal product (ATMP) to treat solid tumors

             PRINCIPAL INVESTIGATOR:                                    Pharma - ATMP
             Prof. Dr. Gabriele Pecher
             Charité                                                        Oncology

SUMMARY                                                   PROJECT GOALS
So far, there is no cure for instance for patients with
                                                          • Complete the preclinical
metastatic breast or pancreatic cancer and new
therapies are urgently needed. The project aims             development of the ATMP
to develop a novel ATMP for the therapy of solid          • Prepare phase I / II clinical trial
tumors. The group will use the innovative ATMP in         • File novel patent

                                                                                                  Track 2
order to generate optimized immune cells to fight
the immunosuppressive microenvironment of solid
                                                          LONG-TERM GOALS
tumors. The ATMP will be validated and preclinical
testing will be accomplished.
                                                          • Perform phase I / II clinical trial
                                                          • License to Pharma or startup
                                                            foundation

                                                     25
A novel gene therapy for treatment of aggressive B cell lymphoma
                                  PRINCIPAL INVESTIGATOR:
                                  Prof. Dr. Antonio Pezzutto                    Pharma - ATMP
                                  PD Dr. Antonia Busse                             Oncology
                                  Charité

          SUMMARY                                                 PROJECT GOALS
          The project seeks to complete the preclinical
                                                                  • Complete the preclinical
          characterization of a human-derived T cell receptor
          (TCR) that selectively recognizes a specific point        development of the ATMP
          mutation of the protein MyD88. This specific mutation   • Prepare phase I clinical trial
          is a key oncogenic driver event in around 20% of        • Establish industry partnership
Track 2

          patients with an aggressive variant of Diffuse Large
          B cell lymphoma, and in around 50% of patients with
          Primary CNS lymphoma. Both patient populations          LONG-TERM GOALS
          have a poor prognosis, and only limited therapies
          are available especially for the elderly and patients   • Perform phase I clinical trial
          with severe comorbidities. Adoptive T cell therapy
                                                                  • License to Pharma
          with MyD88-specific T cells would represent a truly
          tumor-specific therapy, being much more selective
          than CAR T cells or immune checkpoint inhibitors.

                                                             26
GrOwnValve – Anchoring mechanism for a personalized, autologous heart
valve for children
             PRINCIPAL INVESTIGATOR:                                 Medtech
             PD Dr. Boris Schmitt
             Charité                                                    Cardiology

SUMMARY                                                 PROJECT GOALS
The aim of the project is the production and testing
                                                        • Perform preclinical testing of
of an anchoring mechanism of a personalized,
autologous heart valve for children enabling growth       anchoring mechanism together with
in a once-in-a-lifetime point-of-care minimally           the valve
invasive implantation. The novel anchoring              • Prepare phase II clinical trial in

                                                                                                 Track 2
mechanism facilitates placement of the valve without      children
hindering growth of valve and vessel. For babies
born with a congenital heart valve defect there is no
dedicated child valve on the market. Instead they       LONG-TERM GOALS
often receive xenogenic animal valves which degrade
over the following years urging for risky open-heart    • Perform phase II clinical trial in
re-surgery.                                               children
                                                        • Start-up foundation
                                                        • CE certification as a medical device

                                                   27
In vivo validation of a novel class of pain medication

                                  PRINCIPAL INVESTIGATOR:
                                  Dr. Viola Seitz                                Pharma - small molecule
                                  Prof. Dr. Christoph Stein                         Pain
                                  Charité

          SUMMARY                                                  PROJECT GOALS
          The project seeks to complete external validation of
                                                                   • External validation of preclinical in
          in vivo data on NFEPP, a novel compound that has
          demonstrated potent pain relief without addiction          vivo studies
          potential in initial experiments. A patent has been      • Secure follow-on applied research
          filed and results were published in Science in 2017.       funding
Track 2

          Although pain research has identified a plethora
          of targets, no truly innovative analgesics have
          reached the market in the past years, mostly due         LONG-TERM GOALS
          to low efficacy or severe side effects. This leaves a
          significant unmet medical need for novel, safe and       • Further develop under CMC and GMP
          effective compounds with reduced side effect burden
                                                                     conditions
          and abuse liability.
                                                                   • Test safety & toxicity of NFEPP
                                                                   • Perform phase I/IIa clinical trials
                                                                   • License to Pharma

                                                              28
SPARK-BIH
                  Projects

                                                   Track 2
Our SPARK Teams that started funding & mentoring
in 2015 - 2018
                        29
Development of a platform for the isolation of T cell receptors for cancer
       immunotherapy
                               PRINCIPAL INVESTIGATOR:
                               Dr. Felix Lorenz, Dr. Julian Clauss, Dr. Inan         Pharma - ATMP
                               Edes, Prof. Dr. Wolfgang Uckert                          Oncology
                               Max Delbrück Center for Molecular Medicine

       SUMMARY                                                         PROJECT ACHIEVEMENTS
       The project is designed to develop a high throughput
                                                                       DURING & AFTER SPARK
       platform to identify T cell receptors (TCRs) specific
       for cancer antigens to target new patient groups                 • Robust platform established to
       with TCR immunotherapy. Preliminary studies not                    develop >30 isolated TCRs
       only demonstrated the feasibility of the strategy,               • Multiple patents filed from 2015-2019
       but also identified two novel TCRs. Patents covering
2015

                                                                        • Winner at life sciences and
       these TCRs and the platform were previously filed at
                                                                          healthcare startup accelerator
       the European Patent Office. The team is setting up
       a startup (called Captain T Cell) and has acquired                 OneStart in 2016
       follow-up funding to further pursue the strategy                 • Jury price at BioVaria showcasing
       and develop TCRs for the use in patients as well                   event for life science technologies in
       as increasing the output of this novel and unique                  2017
       platform. A service lab (Helmholtz Innovation Lab)
                                                                        • Total follow-on pre-seed funding of
       has been established in parallel at the Max-Delbrück-
       Center.                                                            4 Mio. € until 2020
                                                                        • Startup planned for 2020

                                                          30
“SPARK was the starting point for my whole team to start thinking how we
  can translate our research results in developing drugs for patients.“

“I was so excited to participate in the SPARK mentoring program, because
  it provides a completely new perspective on the clinical translation of
projects. For scientists it is so important to get insights into the process of
    translating basic research findings into treatments. These insights
  provided by the SPARK program definitely shaped my way of thinking
                about current and future scientific projects.”

                              Dr. Felix Lorenz

                                       31
“SPARK enabled us to translate an initial mechanistic idea into a
          successful preclinical drug development project.“

    “SPARK is a great initiative to de-risk innovative projects and to
enhance translational research from bench to bedside. SPARK provided us
  with excellent partners, pushed our project and helped a lot in making
                decisions and focusing on the next steps.”

                                                  PD Dr. Karoline Krause

                                    32
New treatment strategies by targeting the inflammasome

             PRINCIPAL INVESTIGATOR:                                 Pharma - small molecule
             PD Dr. Karoline Krause
             Charité                                                    Dermatology

SUMMARY                                                 PROJECT ACHIEVEMENTS
The project has identified several inhibitors of
                                                        DURING & AFTER SPARK
inflammasome activation in a high-content screen.
Inflammasome activation is a hallmark of several        • Identified several lead candidates
monogenic and complex systemic auto-inflammatory        • Extended indication & initiated
diseases for which only few standard therapies exist.     collaboration
In addition, inflammasome activation plays a central

                                                                                                  2015
                                                        • Preclinical proof of concept in human
role in the pathogenesis of additional diseases such
                                                          skin models
as contact dermatitis. The identified inhibitors are
evaluated for their use in the different indications.   • Patent filing planned for 2020
One compound has the potential to be repurposed.        • Started writing Investigator’s
                                                          brochure
                                                        • Started partnering with Pharma
                                                          concerning novel chemical entity

                                                   33
Gene therapy for the treatment of temporal lobe epilepsy
                                PRINCIPAL INVESTIGATOR:
                                Prof. Regine Heilbronn                               Pharma - small molecule
                                Prof. Christoph Schwarzer                               Neurology
                                Charité & Medizinische Universität Innsbruck

       SUMMARY                                                        PROJECT ACHIEVEMENTS
       The project aims at developing a gene therapy for the
                                                                      DURING & AFTER SPARK
       treatment of drug-resistant focal epilepsy. An adeno-
       associated viral (AAV) vector will be delivered to the          • Patents filed in 2016
       epileptic focus, re-expressing a neuropeptide that              • Preclinical Proof-of-concept in vivo
       will be released in an activity-dependent manner, i.e.            and human brain tissue ex vivo in
       in periods of high neuronal activity which precedes
2015

                                                                         2016
       the onset of a seizure. Suppression of neuronal
                                                                       • Secured GoBio funding of 3.9 Mio. €
       excitability thereby suppresses the epileptic event.
       Strong proof of concept data in mice and rats have                in 2018 for 3 years
       supported the feasibility of this strategy. The team            • GMP production in preparation
       is setting up a startup and has acquired follow-up              • Startup planned for 2021
       funding to further pursue the strategy and develop
       the gene therapy for the use in patients.

                                                           34
“When first invited, I came for money. Now I come for priceless
             expertise and multi-level support.“

                                    Prof. Christoph Schwarzer

                               35
FiXatas - Ready-to use surgical knots

                    PRINCIPAL INVESTIGATOR:                                 Medtech
                    Dr. Panagiotis Fikatas
                    Charité                                                    Surgery

       SUMMARY                                                 PROJECT ACHIEVEMENTS
       In the project a device and method for the generation
                                                               DURING & AFTER SPARK
       of extra corporally pre-tied surgical knots has been
       developed. The device consists of a yarn carrier with   • Patent granted in 2018
       a pre-tied but still open knot ready to use during      • Project developed from invention to
       surgery. It is easy to use even by non-surgeons           marketable product
       without special training. Knots produced are stronger
2016
2016

                                                               • Winner of the Ethicon Future Award
       and more stable than other sliding knots and tying
                                                                 2016
       is faster. Potential user groups have been extended.
       The first use field will be endoscopic surgery where    • 3rd Place of PROFUND “Research to
       tying knots is very challenging due to limitations        Market Challenge 2017”, 2nd Place at
       in space and the visual field. Several patents and        BPW 2018 contest, 2nd Place at YES!
       designs have been filed. The team has founded a           Delft Pitching 2019
       startup in early 2020.
                                                               • Started negotiations with medtech
                                                               • Startup founded in 2020

                                                          36
Lead optimization of STOML3 inhibitors for the treatment of neuropathic pain

                              PRINCIPAL INVESTIGATOR:
                                                                                    Pharma - small molecule
                              Prof. Dr. Gary Lewin,
                              Dr. Christiane Wetzel                                    Pain
                              Max Delbrück Center for Molecular Medicine

SUMMARY                                                        PROJECT ACHIEVEMENTS
In this project a small molecule inhibitor for STOML3
                                                               DURING & AFTER SPARK
will be developed to treat neuropathic pain. The
protein is required for the transduction of pain signals        •   Preclinical proof-of-concept in 2016
in peripheral pain receptors. STOML3 expression                 •   Patent filed in 2016
is upregulated after nerve injury in sensory fibers             •   Publication: 2017
making it a great target. In a high throughput screen

                                                                                                              2015
                                                                •   Secured Helmholtz Validation Fund
several inhibitors of STOML3 oligomerization and
                                                                    in 2016 for further development and
thus (mechano)transduction were identified. In vivo
proof of concept has been achieved in two mouse                     optimization of lead compounds
models for neuropathic pain. Neuropathic pain                       candidates
is a condition caused by nerve damage or disease
affecting the nervous system. In half of the patients
pain relief cannot be achieved by current treatment
options.

                                                      37
Validation study for cervical HPV and dysplasia screening test

                    PRINCIPAL INVESTIGATOR:                                    In Vitro Diagnostic
                    PD Dr. Andreas Kaufmann
                    Charité                                                      Oncology

       SUMMARY                                                    PROJECT ACHIEVEMENTS
       The team has developed a diagnostic test for
                                                                  DURING & AFTER SPARK
       cervical HPV infection and dysplasia detection with
       high sensitivity, specificity as well as a high positive   • Developed a multiplexed
       predictive value. The initial use is in triaging of          quantitative mRNA-based test
       equivocal screening findings. Current tests like             combining HPV and biomarker
       cytology and PCR-based HPV testing either lack
2016
2016

                                                                    expression
       diagnostic accuracy or require a biopsy in follow up.
                                                                  • Developed algorithm to predict
       After patenting, the team is currently performing a
       clinical study. In the future, CE certification of the       disease stage
       test and accreditation of a service lab are planned to     • Patent filed in 2019
       bring the test to the patients. Cervical cancer is the     • Study planned and initiated
       second most common cancer in women living in low
       and middle income countries with more than half a
       million new cases in 2018. Due to lack in standard
       screening procedures the test could be used there
       as a screening tool.

                                                             38
“SPARK has fostered an outside view on our IVD product helping to
   consider critical aspects of development and marketing. “

                                          PD Dr. Andreas Kaufmann
Inhibitors of ribosome assembly

                    PRINCIPAL INVESTIGATOR:                                   Pharma - small moelcule
                    Dr. Rainer Nikolay
                    Charité                                                      Infection

       SUMMARY                                                  PROJECT ACHIEVEMENTS
                                                                DURING & AFTER SPARK
       In this project it is planned to develop a new class
       of antibiotics, based on the inhibition of prokaryotic   • HTS was performed at the FMP
       ribosome assembly. According to the WHO antibiotic       • Due to low specificity of the
       resistance is a global threat. The team has developed      screening assay hit candidates could
       an in-vivo screening assay based on reporter strains,
2016
2016

                                                                  not be identified
       where large and small ribosomal subunits have
                                                                • Advise to improve the screening
       been tagged with red or green fluorescent proteins.
       A disturbance in subunit assembly can be detected          assay & evaluate alternative
       via the fluorescent ratio. Based on this fluorescence-     approaches (e.g. structure-based
       based reporter assay, a high throughput screen was         design)
       performed to identify small molecule inhibitors that     • Identified hit compounds in in-silico
       specifically interfere with the assembly of either the
                                                                  structure-based design methods in
       large or the small ribosomal subunit and thereby
       inhibit bacterial growth.                                  collaboration with AG-Wolber (FU
                                                                  Berlin)
                                                                • Hit compounds are being tested in
                                                                  several assays.

                                                           40
We build muscles– the human muscle stem cell
                        PRINCIPAL INVESTIGATOR:
                        Prof. Dr. Simone Spuler                      Pharma - ATMP
                        Dr. Verena Schöwel                              Stem cells – Muscle repair
                        MDC & Charité

                                                        PROJECT ACHIEVEMENTS
SUMMARY                                                 DURING & AFTER SPARK

Muscle wasting and weakness are leading symptoms        • Preclinical Proof-of-concept,
of a wide variety of diseases. The entire muscle is       preclinical safety ongoing, PEI
affected or only single muscles do not function,
yet with dramatic impairment of life quality and          scientific advice meetings
life-threatening consequences. Muscle diseases are      • Planning of phase I/IIa clinical trial

                                                                                                     2016
untreatable. In Europe alone, over 6 million citizens   • Follow-on funding acquired:
are affected. The team MyoPax develops an innovative      Helmholtz Enterprise 2018-2019, IBB
autologous muscle stem cell therapy to treat muscle       Coaching Bonus 2019, Translatorik
wasting. The team’s technological innovation
enables highly standardized manufacturing of              program of the Else Kröner-Fresenius
pure, native and highly regenerative muscle stem          Foundation 2019-2020
cell populations out of small human muscle tissue       • Science4Life award 2019 for “MyoPax”
specimens. This enables the team to set up multiple       business concept
treatment algorithms for acquired and inherited         • Charité Entrepreneurship Summit
muscle diseases. The team has acquired follow-up
funding and prepares to set up a startup company to       pitch award winner 2019
clinically pursue the development of their approach     • Pitch contribution at Bio-Europe 2017
to fight muscle diseases.                                 and World Health Summit 2019

                                                   41
matrix for antigen-specific secetion of plasma cells secreting pathogenic
       autoantibodies
                     PRINCIPAL INVESTIGATOR:                                  Pharma - small moelcule
                     Prof. Dr. Falk Hiepe
                     Charité                                                     Immunology

        SUMMARY                                                  PROJECT ACHIEVEMENTS
                                                                 DURING & AFTER SPARK
        Long-lived memory plasma cells secreting pathogenic
        antibodies have emerged as a promising therapeutic       • Completed the SPARK funding period
        target since these cells are resistant to conventional     successfully
        immunosuppressive drugs and therapies targeting B        • Winner of the Sanofi iAward 2018 &
        cells. Current therapies targeting plasma cells such
2016
2016

                                                                   2020
        as proteasome inhibitors deplete all plasma cells
                                                                 • Project projected to reach preclinical
        including those contributing to humoral immunity
        that may result in immuno-deficiency. Therefore,           proof of concept by 2025
        the group developed a concept that is able to
        deplete plasma cells based on the specificity of
        their secreted antibodies. The group aims to use
        deplete autoantibody-secreting plasma cells in a
        murine autoimmune model in order to demonstrate
        functionality of the technique. The project recently
        gained interest and support by industry.

                                                            42
“The SPARK program was absolutely                    “SPARK is fundamental for
    decisive to change our mindset in             researchers from any field to bring an
  planning and thinking of experiments           idea from research to what needs to be
and research, from being limited to basic              done in the business field.“
 research to a holistic understanding of
    the requirements of translational                            Dr. Alessandro Faragli
                research.“

                    Dr. Philipp Enghard

                                            43
Flurinocyte - urine flow cytometry as biomarker for renal diseases

                      PRINCIPAL INVESTIGATOR:                                  In vitro Diagnostic
                      Dr. Philipp Enghard
                      Charité                                                     Nephrology

         SUMMARY                                                  PROJECT ACHIEVEMENTS
                                                                  DURING & AFTER SPARK
         The project aims at developing a diagnostic assay
         to quantify cellular components present in human         • Data validation in different patient
         urine via flow cytometry. Cells identified and             groups
         quantified allow the differential diagnosis of several   • Established an easy-to-use sample
         renal diseases. The presence or absence of specific
  2016
  2016
  2017
  2017

                                                                    conservation protocol to simplify
         cell types correlated to disease activity and disease
2015

                                                                    the test logistics
         severity. This simple urine test could be used as a
         diagnostic tool, to screen patients who need a renal     • Currently validating marker and
         biopsy, monitor treatment and predict outcome. The         sample logistics in two multi-center
         assay could become a helpful tool in the clinic when       studies on renal
         a quick primary assessment is required to define           diseases
         subsequent clinical workup and may enable a more
         personalized treatment.

                                                             44
Prediction and prevention of congestive events in heart failure patients

                    INVESTIGATOR:                                              Digital Health
                    Dr. Alessandro Faragli
                    Charité                                                       Cardiology

       SUMMARY                                                   PROJECT ACHIEVEMENTS
                                                                 DURING & AFTER SPARK
       Heart failure (HF) represents the leading cause of
       hospitalization worldwide. Because of the difficulty in   • Risk predictors identified
       treating this chronic disease, re-hospitalizations are    • First algorithm designed
       associated with high cost for the healthcare systems,
       accounting for €28 billion per year in Europe only.       LONG-TERM GOALS
2016

                                                                                                         2017
2017

       The team aims at building an algorithm to predict and
       prevent congestive events in heart failure patients.      • Perform clinical study to determine
       They have identified risk predictors and created an
                                                                   accuracy of prediction algorithm
       algorithm. At the moment, the team is performing a
       database analysis on existing cohorts of HF patients      • Submit invention disclosure
       to build the first risk prediction model.                 • License to medtech or startup
                                                                   foundation

                                                            45
Novel drugs strengthening endogenous immuno-regulatory processes

                     PRINCIPAL INVESTIGATOR:
                                                                                Pharma - small molecule
                     Dr. Stefan Frischbutter
                     Charité & German Rheumatism Research Center                   Immunology

         SUMMARY                                                   PROJECT ACHIEVEMENTS
                                                                   DURING & AFTER SPARK
         The balance in the immune system between
         suppression or activation of immune responses             • Hits from drug screen have been
         is highly complex, very tightly regulated and               validated and immune responses
         fine-tuned with multiple cell types orchestrated.           were partially dissected
         If this fine-tuning is out of balance, diseases such
  2016
  2016
  2017
  2017

                                                                   • Target validation and drug
         as autoimmunity occur. In this project the team
2015

                                                                     development under way
         is focusing on the suppressive capacity of the
         immune system and is evaluating the use of drugs          • Major hurdles have been identified
         to bring this arm back in balance. The team has             in pursuing the idea into the clinic
         developed a high-throughput-screening platform
         and identified already several bioactive molecules
         with re-balancing capacity. The team has validated
         these drug candidates in primary human immune
         cells and assessed the resulting immune reaction
         and potential impact on disease.

                                                           46
BodyTime - A new diagnostic tool to assess the internal clock

                       PRINCIPAL INVESTIGATOR:                                    In vitro Diagnostic
                       Prof. Dr. Achim Kramer
                       Charité                                                       Other

         SUMMARY                                                     PROJECT ACHIEVEMENTS
                                                                     DURING & AFTER SPARK
         The circadian clock is a biological program that
         structures physiology and behaviour according to            • Identified core set of time-telling
         the time of day. It is active in practically all cells of     genes
         our bodies. The circadian clock is thus a cell-based        • Patent filed in 2018
         program that is essential to health and well-being.
  2016

                                                                                                             2017
  2017

                                                                     • Developed a robust assay and
         The team has developed a new diagnostic tool to
2015

                                                                       predictive algorithm with 30 min
         probe human internal time and rhythm using a single
         blood sample. It has utility in defining the correct          accuracy
         time of day for drug dosing, in order to achieve the        • Follow-on applied research funding
         least adverse effects. Of note, >50% of the top selling       by BIH Digital Health Accelerator
         drugs target clock-controlled genes and thus likely         • Started beta-testing with different
         have specific time of day effectiveness. This solution
                                                                       patient cohorts in 2019
         can therefore offer value in reducing side effects
         as well as helping with sleep disorders or work             • Startup foundation planned in late
         performance.                                                  2020

                                                                47
“Before entering the SPARK              “We are very thankful to SPARK
program, we had many translational          for laying in front of us the whole
 paths in mind. Now we have found       spectrum of expertise in the field of drug
     the most promising one.“             development and giving us access to
                                         role-models in the field conveying that
              Dr. Stefan Frischbutter             “we can do it” as well.“

                                                       Prof. Dr. Markus Schülke
“Through the educational and entrepreneurial forum I profited from
        experts and was trained in bringing therapy into clinic.
      I also got insights into hurdles, developmental processes,
        regulations that other SPARK projects are dealing with.
The financial support allowed us to carry on the translational process
of our project. Brainstorming for solving unexpected reactivity of our
             reagent was finally crucial to save the whole
                                project.“
								Dr. Simone Rhein
TCR gene therapy of CD22-positive B cell malignancies
                               PRINCIPAL INVESTIGATOR:
                               Dr. Simone Rhein                             Pharma - ATMP
                               Prof. Antonio Pezzutto                          Oncology
                               Charité

       SUMMARY                                                 PROJECT ACHIEVEMENTS
                                                               DURING & AFTER SPARK
       In this project, the goal is to generate a TCR for
       gene therapy of B cell malignancies by targeting        • novel CD22-specific TCRs identified
       the B cell antigen CD22. CD22 is a good alternative     • patent filed in 2018 (second TCR
       target to CD19- and CD20-directed therapies as            added in 2019)
       these therapies often lead to downregulation
2018
2016

       or loss of the antigen. CD22-targeted CAR T cells
       induce remission in B-ALL that is naive or resistant    LONG-TERM GOALS
       to CD19-targeted CAR immunotherapy. The clinical
       success however is hampered by downregulation of        • Demonstration of superiority over
       surface CD22 expression upon CAR treatment, which
                                                                 CD22 CAR T cells
       greatly reduces efficacy. Since TCRs do not depend
       on antigen surface expression, these patients could     • Perform phase I clinical trial
       benefit from TCR T cell therapy. A newly generated      • License to Pharma
       TCR candidate is being tested for off-target toxicity
       and will be compared to CD22 CAR T cells. A patent
       has been filed on the CD22-specific TCR.

                                                          50
Drug discovery for mitochondrially inherited Leigh syndrome (MILS)
                         PRINCIPAL INVESTIGATORS:
                         Prof. Dr. Alessandro Prigione               Pharma – small molecule
                         Prof. Dr. Markus Schülke                      Neurology
                         MDC & Charité

 SUMMARY                                                 PROJECT ACHIEVEMENTS
                                                         DURING & AFTER SPARK
 The team has developed a novel assay system
 based on patient-derived induced pluripotent stem       • Identified and validated compound
 cells (iPSCs) to identify compounds for treating          class for treatment of Leigh
 Leigh syndrome. Using this assay, a class of drugs        syndrome
 applicable for repurposing that restore the cellular

                                                                                               2018
                                                         • Performed compassionate treatment
 disease phenotype has been identified. The team
                                                         • Plan to prepare phase I/II orphan
 has initiated a compassionate use treatment for
 a terminal ill patient. The patient has recovered         drug repurposing trial
 significantly. Based on these results a clinical
 study is planned. Leigh syndrome is a rare severe
 mitochondrial disease affecting children where
 treatment options are lacking.

                                                    51
“SPARK is a great platform to learn about the drug development
            process and to think as a translational researcher.
 It exposed us to topics which we as basic scientists typically do not have
on our daily agenda but which are vital for translation, such as intellectual
            property and requirements for clinical trial design.
Advice from other SPARKees was helpful in streamlining the way towards a
       drug and to identify important checkpoints within preclinical
                               validation.“

                                               Prof. Dr. Chiara Romagnani

                                      52
Peptide-based vaccination targeting innate responses against viral
infection and cancer
            PRINCIPAL INVESTIGATOR:                                    Pharma – small molecule
            Prof. Dr. Chiara Romagnani
            Charité & German Rheumatism Research Centre                  Oncology

SUMMARY                                                   PROJECT ACHIEVEMENTS
                                                          DURING & AFTER SPARK
The immune system has evolved different strategies
to prevent and fight cancer and infections. Natural       • Co-stimulants assessed for vaccine
Killer (NK) cells are an innate immune cell type            development
able to kill tumor and/or infected cells. The team        • Partners for development of vaccine
has identified a specific peptide whose expression

                                                                                                  2018
                                                            identified
is shared by cytomegalovirus and certain tumors.
                                                          • Clinical indication and potential
The project aims to exploit this immunological
phenomenon by using the peptide as a vaccine                clinical partners identified
directed against tumors and cytomegalovirus,              • In-vivo proof-of-concept ongoing
simultaneously. The advantage of this approach is
that cancer patients can benefit from this boost for
the immune system that is ready not only to fight
cytomegalovirus but also relapsing tumors.

                                                  53
Molecular imaging of biofilm infections - Validation of FISH controls for
       automated endocarditis diagnostics
                                PRINCIPAL INVESTIGATORS:
                                PD Dr. Annette Moter                          In Vitro Diagnostic
                                Dr. Judith Kikhney                               Infection
                                Charité

       SUMMARY                                                   PROJECT ACHIEVEMENTS
                                                                 DURING & AFTER SPARK
       Fluorescence in situ hybridization (FISH) is a
       molecular technique, which allows identification          • Design and validation of controls
       and visualization of microorganisms within tissues.       • Developed a sample tracking
       Currently, the daily diagnostic use of FISH is              software
       restricted to highly specialized laboratories because
2018

                                                                 • Currently developing
       it involves not only high-level of expertise, but also
                                                                   semi-automated digital image
       many hands-on steps, time-consuming microscopy,
       laborious annotation and documentation of FISH              analysis for detection of bacteria in
       images and is lacking standard high quality controls.       histological sections
       In this project diagnostic use of FISH in daily routine   • Developed an intelligent
       for endocarditis diagnostics is tested by automating        image handling archiving and
       the full process of this technique. The group is
                                                                   documentation system
       focusing on multiple aspects of this diagnostic
       procedure – with one emphasis on the generation of        • Currently testing entire platform in
       solid and validated routine positive controls.              routine diagnostic and comparing
                                                                   the ‘hands-on’ with the automated
                                                                   FISH (within the BMBF-funded iSOLID
                                                                   consortium)
                                                            54
“Without financial support, the
 project would not have been possible and the fantastic SPARK
team helped us to achieve tremendous progress in a structured
                    and well-focues way.“

                                             Dr. Kostja Renko

                              55
Image-based Support of Minimal-Invasive Mitral Valve Repair

                    PRINCIPAL INVESTIGATOR:                                    Digital Health
                    Prof. Dr. Anja Hennemuth
                    Charité & German Rheumatism Research Centre                   Cardiology

       SUMMARY                                                    PROJECT ACHIEVEMENTS
                                                                  DURING & AFTER SPARK
       About 7000 isolated mitral valve surgeries are
       performed in Germany every year. Mitral valve repair       • Started development of software
       (MVR) is superior to valve replacement. Successful           modules for image fusion and
       repair does not only lead to better survival but also        integrated visualization and
       better quality of life and avoidance of anticoagulants.
2018

                                                                    interaction
       However MVR success rates strongly correlate with the
                                                                  • Started setting up quality
       experience of the surgeon as MVR is difficult to learn
       due to differences in pre-OP images of the moving            management and documentation
       heart and during the operation (or during surgery).          system
       This indicates the need for a better intraoperative        • Initiated collaborations to specify
       decision support. The team works on the application          user needs and interface questions
       of image-based surgery planning and image-based
                                                                  • Initiated industry collaborations for
       navigation with different modalities. This could help
       the surgeon to accurately consider anatomical and            clinical integration
       dynamic properties of the valve during surgery.            • Acquired BMBF funding together with
                                                                    industry partner

                                                            56
Predicting post-operative complications in real-time

                                PRINCIPAL INVESTIGATOR:
                                                                               Digital Health
                                Dr. Alexander Meyer
                                Prof. Dr. Volkmar Falk                            Cardiology
                                Charité & DHZB

       SUMMARY                                                    PROJECT ACHIEVEMENTS DURING
                                                                  & AFTER SPARK
       The large number of concurrent patient data in
       critical care units goes well beyond the capacity of the   • Prototype ready including user interface
       intensive care physician and may lead to treatment           and client-server infrastructure
       delays or clinical errors. The team applies deep
       machine learning methods in a critical care scenario       • Business plan completed

                                                                                                               2018
2018

       to provide timely and highly accurate decision             • Collected first user feedback
       support to the clinical staff. They have developed a       • Completed team
       set of forward-facing real-time prediction models for      • Started recruiting partner hospitals
       severe post-cardiothoracic surgery complications.          • Further refined and improved bleeding
       Primary focus is the prediction of postoperative
       bleeding.                                                    model
                                                                  • Started to work towards regulatory
                                                                    approval with experts

                                                             57
Inhibition of thyroid hormone inactivation for cancer treatment

                    PRINCIPAL INVESTIGATOR:
                                                                              Pharma – small molecule
                    Dr. Kostja Renko
                    Prof. Dr. Lutz Schomburg                                    Oncology
                    Charité

       SUMMARY                                                   PROJECT ACHIEVEMENTS
                                                                 DURING & AFTER SPARK
       An initial compound library screen led to a preliminary
       list of hormone modulators. The compound target           • Verification and characterization of
       reportedly plays a role in different cancer entities.       >50 compounds from an HTS approach
       During the SPARK funding period, drug candidates          • Further testing of selected, specific
       were characterized for specificity, potency and
2018

                                                                   candidates on intact cells
       on-cell effects. Furthermore, in silico drug design was
                                                                 • Ongoing validation of candidates in
       started to predict improved candidates. Experimental
       approaches to verify the reported beneficial effects        cancer cell lines
       in a cancer cell line completed the overall strategy.     • Plan of strategic cooperations with
       Future plans include strategic cooperation with             oncologists
       oncology experts.

                                                            58
Prevention of paclitaxel-related Neurotoxicity
                         PRINCIPAL INVESTIGATOR:
                         Dr. Wolfgang Böhmerle                         Pharma – small molecule
                         Prof. Dr. Matthias Endres                        Neurology
                         Charité

SUMMARY                                                   PROJECT ACHIEVEMENTS
                                                          DURING & AFTER SPARK
Polyneuropathy is a common, potentially long lasting
and debilitating neurological side effect for cancer      • Assessment and compilation of
patients treated with paclitaxel. It has been shown,        available pre-clinical data
that paclitaxel binds the neuronal-calcium sensor         • Completion of GAP analysis
1 protein which causes calcium dyhomeostasis in

                                                                                                  2018
                                                          • Consultation of BfArM on design
neurons. This process contributes to the development
of paclitaxel-induced neuropathy and can be                 of clinical study
selectively blocked by an approved on–the-market          • Recruitment of clinical partners
drug that can be readily repositioned. In this project,   • Assembly of trial infrastructure
the potential of co-administration of this drug with      • Preparation of documentation and
paclitaxel to prevent neurological side effects is
                                                            design for phase II study
being exploited. Currently the team has designed
a clinical study, consulted the BfARM for scientific      • Funding recruitment in progress for
advice and is recruiting funding for executing the          phase II repurposing trial
study to assess the potential of the repositioned
drug to reduce paclitaxel-induced neurotoxicity.

                                                     59
“SPARK support was essential to continue and to improve our
translational research project. Additionally it opened new horizons to
      evaluate new alternative peptides for our target protein.“

                                                    Prof. Peter Kühnen
MC4R agonist treatment of patients with monogenic obesity

             PRINCIPAL INVESTIGATOR:                                  Pharma – small molecule
             PD Dr. Peter Kühnen
             Charité                                                    Metabolic Disease

SUMMARY                                                  PROJECT ACHIEVEMENTS
                                                         DURING & AFTER SPARK
Obesity is an increasing problem with immense
socioeconomic burden and personal suffering for
the individual patients. In this project the team has    • Patent filed
identified a novel intracellular pathway via a known     • Diagnostic screen established
receptor, how satiety is mediated in the cells. When

                                                                                                 2018
this signaling pathway is disturbed, the patients        • Identified several mutations and
experience a constant hunger feeling irrespective of       epigenetic modifications within the
how much they eat. The goal is to identify patients        MC4R pathway which might identify
that can benefit from modulating the signal with a         patients for MC4R agonist treatment
known drug and change their hunger feeling thus          • Enrolled several patients in the
reducing the weight naturally. The team has identified
patients with several mutations at respective              ongoing Phase 2 investigator-
receptor signaling pathways as well as epigenetic          initiated clinical trial
changes and are able to include these patients in an
investigator-initiated clinical trial.

                                                    61
Combinatorial treatment for metastatic colorectal cancer
                                   PRINCIPAL INVESTIGATOR:
                                   Prof. Dr. Ulrike Stein                       Pharma – small molecule
                                   Prof. Dr. Wolfgang Walther                      Oncology
                                   MDC & Charité

       SUMMARY                                                   PROJECT ACHIEVEMENTS
       Colorectal cancer is the third most diagnosed
                                                                 DURING & AFTER SPARK
       cancer and fourth most common cause of death
       world wide, metastasis being the cause of about           • One patent granted, several patents
       90% of deaths. Team Stein has identified two FDA            pending
       approved drugs that combined robustly inhibit the         • First preclinical developmental steps
       metastasis of colon cancer. They have initiated a first
2018

                                                                   & POC completed
       phase II clinical trial for one of the drugs – and are
                                                                 • Phase II mono-therapy clinical study
       aiming at initiating a second phase II clinical trial
       for combinatorial therapies for colorectal cancer           is running
       (CRC). An option contract has been negotiated with a      • Ongoing licensing negotiations &
       biotech company, which also includes an option for          planned industry partnership
       an industry partnership with the Stein Team.

                                                            62
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