Velabs Therapeutics GmbH –Discovering efficient antibodies with almost no side effects using single-cell droplet microfluidic screening

Antibodies have become key players in modern drug discovery. Several antibody screening formats which currently exist have specific advantages and limitations. Nonetheless, it is always challenging to screen antibodies that bind to cell-surface receptors or target cells. These challenges include as well conventional hybridoma screens that fail to screen more than a thousand clones, taking several weeks until completion, and cost intensity. Another traditional methods, microtiter-plate based formats are dependent on cell proliferation to obtain sufficient amounts of antibodies; therefore, there is very little room to overcome the need for immortalization. All these limitations can be overcome by using droplet microfluidics technology to perform antibody screening. Microfluidics has been increasingly used in the biological sciences as precise and controlled experiments can be conducted at a lower cost and faster pace.

Velabs Therapeutics GmbH is a pioneer and global leader in single-cell droplet microfluidic screening for antibodies. The high-throughput screening platform of Velabs allows testing millions of correctly paired entirely natural Immunoglobulin G (IgGs) from humans and mice for therapeutic effects, rather than just for binding. Rare functional hits are identified, which might be difficult or even impossible using other technologies. Velabs’ antibody screens can significantly and competitively shorten the usual delay in preclinical hit generation and validation from several months or years to considerably shorter times.

In conversation with Dr. Christoph Antz, Managing Director and Co-founder Velabs Therapeutics GmbH

Q. Explain your company’s successful journey to date.

Velabs Therapeutics is a spin-off company founded by Europe’s most renowned life science research institute, the European Molecular Biology Laboratory (EMBL), and its technology transfer arm EMBLEM Technology Transfer GmbH. The institute is a world leader in microfluidic-based screening technology and application. The company is currently hosted on EMBL’s Campus area in Heidelberg. The current active investor is Xlife Sciences AG, a Swiss company focusing on the performance of promising life science technologies. The company is fully operative since 2018 and is focused on fast screening for functional antibodies out of entire natural immune reservoirs. Since the start of operations, Velabs was able to conclude six license and cooperation deals with major global pharma and biotech partners and plans for up to 22 deals by 2021.

Q. What motivated you to establish Velabs Therapeutics, and what makes your company stand out from the competition?

Before Velabs there was no other microfluidic technology available, allowing a 1-step functional screen of millions of B-cells in HTS settings. Even today, Velabs is the only company offering a full unraveling of the complete functional and therapeutic potential of entire immune repertoires within less than 48 hours. Other technologies available explore only the functionality from B-cell sub-pools that only produce antibody binders. Current microfluidic-activities to find neutralizing passive anti-SARS CoV-2 antibodies from convalescent patients start with a first screen for pure binders, which are then assessed in a secondary screen for their anti-viral function. Velabs does that all in 1 single step, i.e., we are the only microfluidic company that has set up an actual phenotypic and functional screen to find therapeutically best anti-viral antibodies with most promising and de-risked developmental profiles.

Velabs is the only company that has established cellular microfluidic HTS assays for a quantitative functional assessment of G-protein-coupled receptors (GPCR) and Ion Channels, based on Ca- or other ion flux induced fluorescence. Like by no other technology, the normalized modulatory strength of B-cell clone antibodies is measured in real-time and serves as a first pass sorting filter. All screened antibodies are synchronously analyzed at identical time points after contact with the target cells, resulting in the best possible S/N ratio.

Q. Even though microfluidic technology has been in this field for around 20 years, there is still room for research and development. What are the anticipated trends or breakthroughs in this?

We believe that we will see a much higher level of multiplexing in the future. For example, we are doing first proof of principle experiments in which an antibody library is screened against several targets in parallel. This will allow us to derive antibodies with increased specificities and decreased side effects. Such approaches could also help to derive cross-reactivity amongst species, e.g., to test efficacy in murine disease models without the need for cost and time-intense modifications or genetic engineering.

Droplet microfluidic technology enables to test antibodies directly on patient-derived cells rather than using cell lines. This allows us to test the functionality in a more physiological setting and opens up the way for personalized treatments. Lastly, we believe that many of the principles currently used for antibody screening will be adapted to discover new synthetic molecules, e.g., using approaches such as DNA Encoded Library Technologies (DELTs)

Q. Artificial Intelligence is the new buzzword; do you think AI has a place of its own in this field?

Definitely, especially when it comes to fast and intelligent choices in sequence/structure optimizations and general correlation analysis in view of optimized exploration of drug efficacy and safety concerning personalized genetic settings, AI is a significant pillar in our current investor’s (Xlife Sciences) portfolio strategy and Velabs actively uses these portfolio synergies to explore proprietary and future process improvements.

Q. What are your plans for the future development of your company?

We are prepared to make Velabs a preferred partner and one-stop-shop for the pharma industry for different aspects of preclinical antibody development, ranging from our superior 1-step functional screening capacities over single-cell sequence analysis of hits to further validation steps like format-engineering, chemical modifications, and general ADMET up to IND. Right now, Velabs prepares for a substantial growth financing to significantly ramp up its current successful low-risk business and to broaden the toolbox by incorporation of best-in-field complementary targets.

Meet the leaders behind the triumph of Velabs Therapeutics GmbH

Dr. Christoph Antz is the Co-founder and serves as the Managing Director of Velabs Therapeutics GmbH. He is an experienced company executive and former venture capital manager in the fields of life sciences with special focus on drug development, diagnostics, and instrumentation.

Before joining Velabs, he was CEO and Managing Director of different companies like Luxendo, Acousia Therapeutics and EMBL Ventures. He holds a Ph.D. in physics (structural biology) from the University of Heidelberg and did postdoctoral studies at the University of California, San Francisco (rational drug development).

Prof. Christoph Merten is the Co-founder and Chief Scientific Advisor of Velabs Therapeutics GmbH. He is a Professor of biomedical microfluidics at the Swiss Federal Institute of Technology (EPFL) in Lausanne, Switzerland. He also holds an adjunct position at the Ludwig Institute for Cancer Research (LICR). He holds a Ph.D. in biochemistry from the University of Frankfurt and did postdoctoral studies at the MRC Laboratory of Molecular Biology (Cambridge, UK) and the Institut de Science et d’Ingénierie Supramoléculaires in Strasbourg,

“We are the only microfluidic company that has set up an actual phenotypic and functional screen to find therapeutically best anti-viral antibodies with the most promising and de-risked developmental profiles.”