LONGREAD. The message came from American entrepreneur Nicholas Vita who has a family member affected by the disease. Looking for a cure for this terrible illness, he had searched for many years, and met with many medical teams, to find a potential treatment. He was amazed by the work by Johan and his team, and inspired by their approach to tackle DBA. The day after their first conversation he flew straight to Lund, Sweden, to make a proposal: start a company dedicated to developing a cure for DBA using the scientific platform that had been developed by Johan Flygare’s team. This marked the beginning of the company Apriligen.
– Right from the start, we agreed that Apriligen should not be run as a typical for-profit company. Our aim is that the profit goes back both to science, and towards making treatments available to families, says Johan Flygare, senior lecturer, Division of Molecular Medicine and Gene Therapy, Lund University.
The purpose of Apriligen is to convert, or ‘translate’, two decades of research at Lund University’s Lund Stem Cell Center into gene therapy treatments for DBA at first, and then into other ultra-rare diseases. DBA is an ultra rare genetic blood disorder that affects the body’s ability to produce red blood cells due to genetic mutations that impact ribosomal proteins. These proteins play an important role in the production of red blood cells, which carry oxygen from the lungs and deliver it to the body. The disease is usually discovered in newborn children, who need to depend on blood transfusions for their survival. However, the blood transfusions the patient receive every few weeks contains large amounts of iron that start to accumulate in the body, which in many cases lead to an organ failure and death. Around 5-7 children per one million is diagnosed with DBA.
The Stem Cell Center is a magnificent incubator that has had enormous success. The innovation and research out of Lund have been incredible, and the Vice-Chancellor extraordinary in his support of us.
Finding the genetic key to DBA
That Johan Flygare even became interested in genetic research to begin with was a fortunate mix of chance and curiosity. It all began during a medical school rotation in the hematology clinic in 1998, where he became aware of ongoing gene therapy research: the idea that one could potentially cure diseases by correcting the underlying genetic defect.
In 2000, Johan started as a PhD-student in professor Stefan Karlsson’s lab, who established the Division of Molecular Medicine at Lund University. This division was later to become one of the foundations for Lund Stem Cell Center – one of the world’s leading centers for this kind of research and development. Here, the work on DBA began in earnest.
Together, Johan Flygare, Stefan Karlsson and their colleagues began work on developing a concept for treating DBA with gene therapy. Their aim was to genetically alter the mutated gene in the stem cells and transfer a healthy copy of the gene back into the blood, using a vector derived from the Human immunodeficiency virus (HIV). The vector uses mechanisms the virus has developed over time, to transport a healthy gene copy permanently into the patient’s genome.
Bringing a gene therapy from the lab bench to life
Precisely at the moment when Johan Flygare and Nicholas Vita met, Johan and his team were at a stage where they could do no more with academic research funding. In order to take the therapy to patients they needed investment to begin work on developing manufacturing protocols, and performing toxicology, quality and safety tests of the therapy. This is not only time consuming, but extraordinarily expensive and requires unique expertise from specialized personnel at every step of the process.
Today Nicholas Vita is the CEO of Apriligen, a role he has had at other companies – including those he has Co-Founded. Since the company was created, they have created a product which is now ready for clinical trials, and developed a process for treating patients. Patient stem cells will be removed in a minimally invasive process by administering growth factors and antibodies which activates the stem cells to leave the body. After the gene transfer process, the stem cells will be frozen down, and quality checked. After about a month, the now healthy stem cells, can be permanently administered back to the patient.
– If everything works as it should, the effect will show within weeks, when the healthy stem cells grow and produce red blood cells, says Johan Flygare.
The team has also been performing efficacy and safety tests in patient cells and animal models, to be able to submit applications for clinical trials to the Swedish Medical Products Agency and the U.S. Food and Drug Administration.
The trial will be set up at several sites including the Skåne University Hospital, Sweden, and hospitals in the Netherlands and in the USA.
Lund’s scientific ecosystem - a catalyst for advanced therapies
Lund Stem Cell Center has been instrumental to the project’s success according to Johan Flygare. This includes the exchange of knowledge with colleagues working on similar projects, the international networks and the multidisciplinary researchers and students. Being part of an environment with a long-term vision has been important, as has the administrative and innovation support.
Nicholas Vita reflects that the open environment at the Stem Cell Center, and at the University, was key to setting up the company.
– The Stem Cell Center is a magnificent incubator that has had enormous success. The innovation and research out of Lund have been incredible, and the Vice-Chancellor extraordinary in his support of us.
In 2024, Apriligen received news that a well known US Venture Capital firm has offered to fund the first clinical trials.
Charting the future toward the clinic
What are Johan and Nicholas’ hopes, now they are on the verge of the next crucial step for Apriligen?
– An immediate wish is for the clinical trials to begin so Apriligen can treat patients and prove that our system not only works – but fundamentally expands the number of ways we can apply our technology, says Johan Flygare.
Since DBA sufferers that rely on chronic blood transfusion only tolerate this treatment for a limited time due to progressive buildup of iron from the donor blood, many children with DBA have to get stem cell transplantations from other donors, a treatment which is harsh, often risky, and does not always work.
Nicholas Vita says that they have three main goals with Apriligen.
– Number one is to show that the therapy works, and that there are better alternatives out there for children to give them back their lives. Number two is to prove to the world that we can create a platform approach to rare disease and gene therapy that allows a degree of scalability, that will not only help researchers get funding, but will also help companies create more efficient and attractive business models.
– Number three is about showing that rare disease can change lives in a profound way, and can be an lucrative investment at the same time. And a final, unofficial goal – the one that drives the team’s passion and dedication, is to validate the trust and confidence we have received from affected children, their parents, the University and the regulators.
Underlying all of their work, is their personal passion and never ceasing motivation for both Johan and Nicholas to help patients to live long, happy and healthy lives.
– From when I first started out as a doctoral student, I knew that I wanted to contribute to better treatments for patients, says Johan Flygare.