Interview | Prof. Dr. Georg N. Duda, Director Julius Wolff Institute and Dr. Garima Bhardwaj Head of the BIH Clinical Incubator

Building a community for bringing advanced and regenerative therapies to the patients

Berlin-Brandenburg is an excellent location for advanced and regenerative therapies (such as gene- and cell-based therapies, GCTs or biomaterial-based approaches). A lot is happening in this field here. Last year, for example, the Bayer/Charité “Berlin Center for Gene and Cell Therapies” opened in June and Bayer Co.Lab relaunched its space in November. On January 20th, the CLIC (BIH’s Clinical Incubator) had its first public event as another highlight for infrastructure and community building in the capital region on advanced and personalized therapies. We spoke with Professor Georg Duda, an expert in building advanced and regenerative therapies, and Garima Bhardwaj from the BIH Clinical Incubator both from the Berlin Institute of Health at Charité about research and developments in the field of advanced and regenerative therapies.

1. The development of advanced and regenerative therapies is very dynamic, with a lot currently happening. What drives you? Where are you active?

Georg Duda: Ever since the BIH Center for Regenerative Therapies was initiated in 2006, we have been developing therapies that boost the body's capacity for endogenous regeneration. There are numerous potential clinical indications for personalized therapies, but we focus on four specific clinical fields (cardiovascular, musculoskeletal, infection and immune-tolerance, and liver regeneration). We selected these clinical topics since we are at Charité internationally very strong positioned in these in basic science as well as in clinical translation. Some organs like the liver or the bones have an intrinsic capacity to self-heal. We try to identify common mechanisms and principles that enable healing without fibrosis. We are basically trying to overcome fibrotic scarring that occurs in some patients and some indications to empower true cure and healing. This is more than just a bioengineering approach “nice to have”: Our current pharmacological therapies treat symptoms in most patients but do not target the underlying problem. To enable quality in years lived for patients we need to move from chronic therapy to real cure whenever possible. This is both a challenge to bioengineering innovation but also to maintaining our health in an ageing society. Most outstanding are our achievements in a number of clinical approval trials to realize cell therapy to for example reboot the immune system in patients undergoing organ transplantations. One way of doing so is to basically reprogram the immune system so that it does not attack the transplanted organ. Another example is the identification of patient at risk to healing: While in most patients you expect fractures to heal. However, in around one in five patients, bone fractures won’t heal by themself. We can identify these patients when they enter the emergency ward and boost their healing capability. Our research empowered cell-based therapies, immune-modulatory strategies, biomaterial-based approaches to guide regeneration or vaccination strategies against infections, iPSCs-based or bioprinted implants to replace organ functions. But once the basic discovery  has been realized, how to bring such ideas to more patients?

Garima Bhardwaj: My capability here is to supplement the scientific expertise and the clinical translational capacities that the Charité hospital and BIH have and support them with the creation of start-ups. I work as the Head of the Clinical Incubator at BIH, where we are trying to boost startup activity out of the Charité, the BIH as well as the wider Berlin ecosystem. This specifically applies to the fields of Advanced Personalized Therapies, such as projects in cell and gene therapy, combination products with biomaterials or any CRISPR technology platforms, RNA vaccines and such. The start-ups stay with us for up to two and a half years, during which time we provide them with fully equipped lab spaces, turnkey operational support, business development and regulatory support, as well as a vibrant international ecosystem to help them raise enough money and secure funding for the next stage of their journey. We enable them to transition from an academic project towards commercialization by forming a start-up and eventually come become an industry.

2. Garima, can you briefly outline the mission, target group and services of the clinical incubator at BIH?

Garima Bhardwaj: The mission of the Clinical Incubator is to support start-ups in the space of Advanced Personalized Therapies and provide them with a safe environment for a clinical de-risking of their projects and acceleration towards startup creation. We are open to both academic projects and early stage start-ups. They come to us when they have raised either pre-seed or seed money. They may have funding from EXIST grants or copilot grants and are looking for their next stage of development. We provide them with a range of services, including on the operational side – a fully equipped lab space. We also provide them with operational support through an experienced site team. And we provide them with entrepreneurial support – we connect them with business development services, which can advise them in terms of market access strategy or grant writing. We also connect them to venture capital and provide showcase activities. And finally, we also support them with regulatory and clinical advising services, providing support not just from the pre-approval to the post-approval stage, but also with scientific writing; and this is a big step in the transition from academia to industry for any clinical product. In addition, we help start-ups raise enough funds to occupy their own facilities and basically function independently as a registered company. During the time we work together, they transform from being a grant-funded academic project into a company that can function independently.

3. And how do you yourself benefit from the regional ecosystem?

Garima Bhardwaj: We have a lot of great projects here, and a lot of potential for the development of Advanced Personalized Therapies. One of the great things that we have within the BIH and Charité is a close co-existence of core research units with clinical units and a kind of natural collaboration and cross-talk that happens between them. This is quite rare and can accelerate the timeline of product development naturally. I speak from my experience over the last 12 years when I say that this kind of environment is difficult to replicate. We are trying to capitalize on that. And the same thing is true for the Berlin ecosystem, where there are a lot of people who are very dedicated to this field. We also try to work together with different institutions and different partners to channel our energies in trying to make Berlin a hub for Advanced Personalized Therapies. As Georg mentioned, Berlin has a deep patient phenotyping expertise with different KOLs (key opinion leaders) who are, luckily for us, within close access. We want to build upon this great foundation and provide all the missing elements; so that they can contribute to company creation as well. And this adds value, not just for our institute, but also for Berlin as an ecosystem. Because once these companies are created, you can attract international talent, and you have more opportunities in terms of economic prosperity for the state and the city.

4. Where do you both see future challenges in this field in Germany?

Georg Duda: There are multiple challenges, in different dimensions but also huge opportunities, no question. While there is for example a global move towards CAR-T cell- based strategies in oncological research and therapy development other clinical indication fields beyond oncology become attractive opportunities. In general, advanced and personalized therapies will be flourishing beyond rare and cancer, where they are now showing their potential. In addition, new technological developments, such as vaccination strategy like the one from BioNTech, emerge and push into new clinical domains. Also 3D printing and bioprinting are gaining substantial momentum. Germany has all bioengineering and technological capabilities to be at the forefront to be globally shaping the “cutting edge”. That makes the efforts of a national strategy cell and gene therapy so important. The BIH aims at helping coordinate all German research and translational activities in cell and gene therapies to really address the key bottle necks in this innovative field. Charité, in cooperation with Bayer, is also building a major hub for translational activities in cell and gene therapy to empower start-ups that want to build their Good Manufacturing Processes towards own production capabilities or scale established GMP capabilities. In addition, we are extending our clinical GMP facility at Charité from so far 6 units to a total of 14 GMP slots, hopefully opening in the coming months. However, there are challenges in terms of feasibility, technology and research that we have to overcome. And it's not easy – you have need to know the medical requirements, and then you have to really move forward in order to complete a successful clinical phase III. It takes a team effort, a long time and also a lot of money. Luckily, we are in a situation, in Germany and in Europe, where public funding opens the possibilities to fund academic clinical trials to de-risk novel therapeutic concepts. However, Germany lacks venture investments that are needed in any later stage of company development and upscaling. Basically, we are trying to do is to increase trust in early academic ideas by using our clinical incubator as a system to de-risk in early start-up phases. So, we will coach acamedic projects from seed to start-up funding and help to de-risk conceptual approaches in such advanced and personalized therapy developments, where big pharma usually does not yet invest. How can we help to make relevant innovative approaches attractive to venture investors? While there is in general enough money in Germany and Europe, we need to bring Germany and Berlin back on the map for such investors and attract more of them.

5. How has the HealthCapital cluster supported your work and activities to date and where do you see future synergies between your work and that of the cluster?

Garima Bhardwaj: The focus in building the Clinical Incubator is not just to support startup activity coming from the BIH and Charité, but also to open it up to the entire Berlin and German ecosystem. The strength of the cluster can really be leveraged here. We want to foster collaboration between different institutes and organizations, all working together to really make this a hub for Advanced Personalized Therapies. And I am confident that we will have regular interactions with the cluster and for example organize regular events together. The incubator will also be open to applicants from different institutes and possibly also from companies that are referred to us by the cluster. So, we hope to continue working together in this manner.

Georg Duda: We have always had very close links with the HealthCapital cluster. There is an overarching interest of the state of Berlin to enhance, support and promote activities and translational efforts and to coordinate them in order to bring them into focus. For example, there is the regular RegMed Forum, where we bring together experts on various topics. It is an excellent platform for hearing and discussing science in the field of regenerative medicine and for networking. The next RegMed Forum will take place on February 27 in Berlin and will focus on ATMP development and translation – Garima will also be one of the speakers there.

In the very beginning, we realized that new regulation for advanced therapies had been published by the EMA, which led to a lot of uncertainty for many companies. And we suddenly became a sort of communication hub, helping companies find the right people to talk to or identify where to actually get knowledge. From the very beginning, together with Berlin Partner, the strategy was basically to try to build a community and form an environment in which to meet the experts. Something like that really helps you as a company. But in the very beginning, it was a lot of lack of knowledge and accessibility, and that is really what shaped the beginning of the whole development. Nowadays, we can look further into the future. The regulatory frame is in place, a lot of the companies have made it and actually succeeded in re-certifying products or getting them into the pathways. The most important thing now is to keep building a community.

I think that we have a sweet spot here in Berlin, but we need to really focus on our key competencies. What makes us substantially different to what we see in the rest of Europe – Britain, Sweden, or Switzerland, just to name a few – is that we are attractive and we can really work together with other European actors. And Berlin Partner and the HealthCapital cluster can really help shape that specificity.

About the person:

Dr. Garima Bhardwaj is the head of the BIH Clinical Incubator at the Berlin Institute of Health (BIH). In this role, her work focuses on supporting life science entrepreneurs and promoting advances in personalized and regenerative medicine. She holds a PhD in Chemical Engineering from Northeastern University in Boston, USA and has extensive experience in various sectors including academia, biotechnology and pharmaceuticals. She has held leadership positions in organizations such as LabCentral and Bayer Pharmaceuticals, where she led strategic partnerships, business development initiatives and community engagement.

Professor Georg Duda is the founding director of the Julius Wolff Institute at the Berlin Institute of Health of the Charité – Universitätsmedizin Berlin, a joint faculty of Humboldt University and Free University of Berlin. He studied Biomedical Engineering at the Technical University in Berlin and obtained his PhD in Biomechanics at the Technical University of Hamburg-Harburg in 1996. After research stays at Mayo Clinic and Johns-Hopkins University he became Head of the Research Department of the Center for Musculoskeletal Surgery (CMSC) at Charité in 1997. In 2020, Professor Duda accepted the position as BIH Chair for Engineering Regenerative Therapies and has been elected Member of the Senate of the German Research Foundation (DFG). Since 2021 he is Speaker of the BIH Center for Regenerative Therapies (BCRT).

Further links: