When the phone call from PhD student Fábio Rosa came through, Professor Filipe Pereira knew that this was the start of something big. All their work had been leading to this moment.
The red cells in the dish were from a mouse, and Filipe and his colleagues had been trying to reprogramme them into dendritic cells, specfically type 1 conventional dendritic cells,
(cDC1s). Dendritic cells are potent antigen-presenting cells that are critical in the iniatation of immune responses to eliminate disease. They play a key role in the fight against cancer since they are considered essential for kickstarting and promoting anti-tumour immunity.
The red hue signified that the reprogramming process had begun. It confirmed that a specific trio of transcription factors (specialized proteins) could be used to reprogram fibroblast cells (skin cells) into dendritic cells. Since cDC1s are very rare in the peripheral blood and tumors, this discovery was important as it opened the door to restoring their presence, something which could be useful in fighting tumors.
– With these initial results, I knew we could proceed. Being able to not only produce dendritic cells, but to reprogram other cells to become such, opened a path to develop completely new immune therapies against cancer, says Filipe Pereira, Professor, Division of Molecular Medicine and Gene Therapy at Lund University.
Shortly after, Filipe submitted a patent application to protect his discovery and the method to identify the three transcription factors. From previous experience and his postdoc stay in the US, he knew it was important to protect the intellectual property early on.
– I had seen that research groups with startup companies were much more dynamic than those without. I also knew that there were other groups working on similar things who were only a few months behind us.
Transitioning from Academia to Startup Venture
Efforts to establish their methods and concepts followed. In 2018, their first scientific study was published in Science Immunology. On the very same day, he created the company Asgard Therapeutics, located at the Smile Incubator in Lund.
– From there on, we had solid proof that our approach would work.
An exciting time started. From 2018 to 2021, Filipe and his research group focused on refining and advancing their methods. They soon realized that their approach could be used to convert tumor cells directly into dendritic cells, with the potential to initiate an immune response against the tumor. However, the immediate next challenge was transferring their reprogramming method from mouse cells to human cells.
– This step was crucial. If we failed, there would be no future for the research, or any new treatments.
His group did succeed; with the help of early investment from LU Holding, they were able to overcome problems connected to low efficiency in the reprogramming of the cells.
– LU Holding supported us at an early stage, enabling us to launch the company properly, with a board, and a clear vision. Without this help, we wouldn’t have been able to become professional so fast.
140 meetings with various investors followed. Some approached Filipe, and some he approached himself. Finally, in 2021, Filipe and his team were able to raise a significant investment round with key venture capital investors.
The Business Case for a Novel Immunotherapy
In 2022, they reached an important milestone, finally managing to improve reprogramming rates for human dendritic cells through fine-tuning and developing their method. This work lead to another seminal article in Science Immunology.
Now they could begin to develop their business case. The immunotherapy AT-108, represents the lead program of Asgard Therapeutics which has the aim to develop it for clinical application. AT-108 uses an adenoviral vector to deliver the three transcription factors identified in 2018 directly into tumors, reprogramming the tumor cells into dendritic cells – triggering an immune response against the tumor. The reprogramming process, currently done in vitro, in laboratory petri dishes, takes about nine days.
– With this early investment we could start to meet some of the benchmarks connected to our technology and approach, answering the question on how to move from in vitro treatments, outside the body, to in vivo treatments, inside the patient, says Filipe Pereira.
– In addition to demonstrating remarkable remissions in tumor models in mice we were also able to show that we could reprogram patient tumor samples into dendritic cells. Before we had only confirmed that our method worked on human model systems, not actual patient samples.
In 2024, Asgard Therapeutics secured a second substantial investment round, bringing the venture arms of two additional pharmaceutical companies on board. Together with the previous three investors, these companies have invested 30 million euros into the company.
How did they manage to gain these very large investments?
Filipe’s answer is very clear:
– The science, the uniqueness of the idea, and its prospects have been most important. Also, our team. Everyone is inspired to find solutions, especially when things are going off track.
Another significant factor in the company’s success has been the support from Lund University’s strategic research areas, including Lund Stem Cell Center, he emphasizes. The center has been instrumental in creating an environment for both the research and the company to develop in a multidisciplinary fashion.
– We have access to the technologies, approaches, and infrastructures needed to deliver on our goals. It’s one thing to have an idea, but you need a structure to go with it too. The Stem Cell Center has provided this structure.
The foundational experiments, and those reprogramming the patient sample cells, were all performed in the center’s laboratories. And as the company has developed, the team has continued to use the flow cytometry instruments available at the center’s FACS Core Facility, to perform the high level of characterization needed to get the product ready for clinical trials.
More than 15 researchers from the Lund Stem Cell Center have been involved in the research supporting the foundation and development of Asgard Therapeutics. Some have also taken on positions within the company.
– To work in a company, you need to both have the academic prowess and ability to capitalise on business opportunities. It has been great to see Cristiana Pires, and Fábio Rosa, a former postdoc and PhD student in my lab, take on key roles not only as co-founders but also as the managing team of Asgard.
– This is what makes Lund Stem Cell Center so special. It gathers a critical mass of researchers that all contribute to this interdisciplinary, multifaceted environment. It means that, together, we always have enough colleagues and students to build and develop an idea. This is really important, not only for us, but for the whole research field.
He adds that the open and supportive workplace environment at the Lund Stem Cell encourages the interface between science and industry - creating opportunities for early-stage companies to generate data that attracts investors.
Looking Ahead
Filipe and his colleagues at Asgard are now occupied with meeting the next milestones in the company’s development, which includes the preparation of safety and toxicologic protocols to clear their immune therapy for clinical trials and in vivo delivery.
– I am glad we have got this far. Running your own company is a huge challenge. You never know if you will reach the next step. It is an unstable situation, and you really need to believe in your idea enough to raise money and motivate your team.
Throughout this journey his own motivation has been sustained by the desire to help cancer patients for whom no successful immune therapies exist, such as those with breast cancer, colorectal cancer, sarcoma, and head and neck cancer.
– At heart I am a fundamental scientist. Getting to this stage and finding solutions to start clinical testing is very exciting to me.
