Barbara Bachler-Konetzki

SHORT SUMMARY OF SCIENTIFIC CAREER

Barbara received her PhD in Biomedicine and Biotechnology from the University of Veterinary Medicine in Vienna, Austria in collaboration with the Harvard Medical School / Dana-Farber Cancer Institute in Boston, USA where she focused on the profiling of protective anti-HIV antibody responses upon vaccination.

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After moving back to Europe, she continued to work on antibodies at MorphoSys, a biotech company based in Munich, Germany, well-known for the discovery and development of therapeutic antibodies using human antibody libraries by applying the in silico phage display technology. During this time, Barbara successfully discovered a novel acting therapeutic antibody, and progressed it all the way from concept to pre-clinical candidate nomination. In 2021, this molecule entered clinical phase 1 testing in immune oncology. Joining Evotec in 2018, she played a key role in the establishment of the streamlined hybridoma platform and the implementation of the ATX-Gx™ mice from Alloy as source of fully human antibodies. She is now leading a group of scientists and technicians supporting internal and external antibody programmes from target identification to lead candidate nomination.

1

What were the limitations of previous hybridoma-based approaches?

Although the development of the hybridoma technology was a landmark event, the methodology still faced the limitation of generating mouse monoclonal antibodies, which are suboptimal as therapeutic agents due to rejection events caused by the human immune system. For example, while OKT3, the first therapeutic mAb against T-cell expressed CD3 has proven effective for preventing host-versus-graft disease, the antibody itself elicited an immune response that resulted in accelerated drug clearance. Later it turned out that this unwanted feature was induced by the non-human sequences of the murine OKT3 antibody. To overcome this problem, researchers developed techniques to transform rodent antibodies into structures that would more closely mimic human antibodies, without the loss of binding or functional properties. First, mouse monoclonal binding sites were combined with human antibody sequences to create so-called chimeric or humanized antibodies. Later, these strategies were even further expanded to create genetically engineered mice to produce antibodies with human sequences, allowing the immunisation of mice with fully-human immune systems (such as the ATX-Gx™ platform from Alloy Therapeutics) and therefore selection of therapeutically well-suited antibodies.

2

What is so special about the ATX-Gx™ mice and how will this collaboration improve the offering for Evotec’s clients?

Alloy Therapeutics is a biotechnology company allowing other companies access to their tools, technologies, and services empowering the global scientific community to make better medicines together. The ATX-Gx™ platform comprises a suite of highly immunocompetent transgenic mouse strains that
allow the selection of fully human antibodies upon immunization with an antigen of choice. For me as a scientist, it was very important that their existing technologies are continuously being improved. As Alloy Therapeutics is re-investing all of their revenue in innovation, I am convinced that this will allow them to grow and expand their human therapeutic antibody discovery platforms going forward. As a matter of fact, they are already working on additional mouse strains, for example the ATX-HyperImmune strain to allow generation of human antibodies against high-homology targets or their ATX-CLC platform, a suite of common light chain mice that allow better and faster bispecific antibody discovery.

The technology partnership between Evotec and Alloy Therapeutics has expanded our existing antibody discovery capabilities, offering a comprehensive service with both in vivo and in vitro technologies. Our clients and collaboration partners will have access to this cutting-edge mouse platform and thereby will enable best-in-class in vivo discovery of fully human monoclonal antibodies across many different disease areas.

3

What is so special about Evotec’s integrated antibody discovery and development approach?

In my experience, companies are usually focusing on the discovery OR the development of novel antibody drug molecules. In the past, companies have successfully developed great antibody libraries, they came up with better ideas of how to efficiently produce mAbs or they were very good in understanding the molecules’ pharmacological behaviour in a certain indication of interest. However, there are not many success stories of where all of these capabilities can be combined under one roof. Three years after joining Evotec, I am still impressed with the breadth of possibilities and the expertise one company can offer to clients or collaboration partners as a contract research organisation. For example, we are currently seeing many virtual companies that approach us to support their highly valuable programme from target validation up to IND and even market access. They trust our knowledge in drug discovery and hand over their precious ideas to turn them into valuable drugs. For integrated programmes that may run over several years, Evotec assembles a project-dedicated team of scientists that supports all of the required activities needed to fully understand the target biology, the mode-of-action needed and the intrinsic features of the generated lead molecules. This allows us scientists and project leaders to build a trustworthy relationship with the client or collaboration partner, and feel closely connected to the programme. I am convinced that this one-stop-shop idea increases the flexibility of the programme and in the end the quality of the resulting product.

4

Tell us about your vision – what do you expect from therapeutic antibodies in the future?

For me the recent COVID-19 pandemic made it clear how advanced research and development has become in the context of therapeutic antibodies. Anti-SARS-CoV- 2 antibodies have been selected from convalescent patient B cells, screened for their broadly neutralizing behaviour, and manufactured for therapeutic application basically in real-time. As a community, we have been getting better, faster and more cost-effective in all of the antibody-relevant technologies, no matter if you look at the advances within the discovery or the manufacturing of biologics. I strongly believe, that with the combination of best-in-class antibody technologies, biomarker discovery, and the support by AI-methods, we will be able to design the next generation of antibody drugs, which will offer even better treatment options and hopefully make a huge difference for patients in the future. I am proud to be part of this journey and excited to see how our integrated offering will transform the discovery and development process of therapeutic antibodies in the near future.