1. Can you talk a bit about how your scientific training and industry experience led to your current role at Memo Therapeutics AG?
I’m a bioengineer by training, and the common thread of my career has been the use of novel technologies to better understand diseases and develop new therapies. I started with a PhD at EPFL, the Swiss Institute of Technology in Lausanne, where I was studying the role of phenotypic heterogeneity on the interactions between host and pathogens. I then moved to Harvard for a post-doc, where I developed microfluidics and microscopy-based technologies to study how antibodies cross the blood-brain barrier.
I then transitioned into industry and joined HiFiBiO, an American startup in Cambridge, MA. I started as a scientist and moved up to leadership positions, where I was involved in the discovery and development of therapeutic antibodies, mostly for oncology. This transition was a revelation for me as I really enjoyed the collaborative way we worked in industry. I find that we’re all committed and focused on this one common goal, and in my case, it’s been drug development.
I joined Memo Therapeutics AG three and a half years ago, where I currently serve as the Head of Oncology Research. Its approach of comprehensively copying the B cell repertoire before screening them was fascinating to me. At Memo Therapeutics AG, I have the chance to work with five brilliant scientists where we discover and develop new treatments for cancer. It’s a small team, but we have this fast-paced approach that makes me believe we can have a significant impact, and that’s what drives me every day.
2. What does a typical day look like for you as Head of Oncology Research?
As for many people, no two days are the same, but they share the common goal of advancing science and developing drugs. I typically start my day by reviewing literature. There’s a lot going on in oncology research and it’s important to be up to date with these discoveries and developments. The rest of my day is usually divided between making direct contributions to the research combined with managerial duties. My direct contributions include next-generation sequencing (NGS) data analysis and right now I’m working hard on establishing channels to source tumor resections from people suffering of cancer. In my role, I serve as the bridge between the long-term, high-level objectives of the company and their practical implementation. This involves translating our strategic goals into actionable plans, ensuring successful and timely execution. Overall, it’s a very dynamic and challenging, but rewarding position.
3. How excited are you about Memo Therapeutics AG’s oncology program and its potential to identify novel antibody-target pairs for the treatment of solid tumours?
I’m incredibly excited about our oncology program and our efforts to identify new antibody-target pairs. There has been great progress in cancer treatments, however, for many cancer types, treatments remain ineffective and are unfortunately often associated with significant side effects.
Sometimes the immune system of people suffering from cancer can successfully mount an immune response against cancer cells and fight it. We aim to understand the mechanisms behind this because we believe that the immune system holds the key to identifying the most effective ways to target cancer cells and eventually developing more effective treatments.
I think we’re well suited for this because we have unique tools at Memo Therapeutics AG to study the immune system, allowing us to potentially have a huge impact on cancer treatments. We’re also committed to sharing our results. It’s something that’s driving us in the team, and with the support of management, we’re aiming to share our discoveries and make contributions to the general field of immunobiology along the way.
4. How does Memo Therapeutics AG differentiate itself from other biotech companies working in the oncology field?
Memo Therapeutics AG is active in two major therapeutic areas: infectious diseases and oncology. This stems from the fact that we have the technology that allows us to discover antibodies efficiently, which can be used to successfully treat both viral infections and cancer.
Oncology is a very competitive field, with many companies studying cancer and aiming to treat it. A major challenge our industry is facing though, is the scarcity of good cancer targets, resulting in most companies focusing on the same approaches. Last year Nature Reviews Drug Discovery reported that there were 56 clinical assets targeting the PD(L)-1, and that over time there are more and more companies focusing on the same targets. We think this is a real problem.
What Memo Therapeutics AG aims to do is to differentiate ourselves by identifying new tumor entities. The beauty of our approach is that along the way we’ll also discover antibodies that can target these cancer antigens. So, at the same time as discovering novel tumor targets, we have antibodies that can hopefully be used for therapeutic purposes.
5. What is the role of tumor-infiltrating B-cells (TIBs) in certain types of cancer?
Tumor-infiltrating B-cells (TIBs) have been shown to be positively associated with prolonged patient survival, for most cancers. This has been seen in lung, colorectal, and ovarian cancer, the three cancer types that we focus on. What was striking is that a few years ago, it was shown that these TIBs also predict responses to immune checkpoint inhibitors, and that was quite surprising as immune checkpoint inhibitors act on T cells and not on B cells.
What’s also interesting about B cells is that they don’t just infiltrate the tumor and act there, they also mature and develop within tumors. In tumors you can have tertiary lymphoid structures, which are sites of B cell development. So naive B cells which arrive there are then presented with surrounding cancer antigens, and then these B cells can develop, mature and secrete antibodies. The function of these antibodies is still under investigation. However, recent findings have shown that these B cells can have direct antitumor activity by way of the secreted antibodies recruiting immune cells to kill cancer cells.
6. How is Memo Therapeutics AG’s DROPZYLLA® technology suited to mine the antibody repertoires of TIBs from elite responders?
Of course, research on B cells and cancer has been going on for some time before us. However, it remains a huge challenge to study B cells in cancer. There are two main challenges when working on TIBs. One is the scale; there are a lot of B cells in tumors, sometimes expressing millions of distinct antibodies. You need methods that allow you to comprehensively and efficiently assess the functionality of all these antibodies. Not all antibodies in a tumor have the potential to become therapeutics and so it’s important to design clever assays to screen for them. You can easily sequence a lot of B cells, but then all you get is their sequence and you’re limited in understanding the function of the antibodies they secrete. That’s where Memo Therapeutics AG’s platform comes in. It’s high throughput so we can screen millions of B cells efficiently using complex cell-based or proteomic-based assays.
The other aspect that’s complicated about studying TIBs is that they’re fragile and short lived. Most technologies that allow you to study B cells are not adapted to studying B cells in cancer, especially when you don’t know the antigens they target, or what their role is. This is overcome with our DROPYZLLA® platform at Memo Therapeutics AG. Using our industry-leading technology, we can immediately get those tumor resections from donors with superior immune responses, isolate the B cells and then biobank the antibody repertoire and recombinantly express it in immortal cells that are incredibly robust so we can have them stored indefinitely for repeated future use. We then have plenty of time to actively screen these antibodies with complex methods to find out which ones are best suited to be developed into therapeutic antibodies.
