Norwegian doctors prepare for Idogen’s study
Biotech company Idogen is in full swing with preparations for the first clinical study with the cell therapy IDO 8 in patients with severe haemophilia A. BioStock had the opportunity to interview Professor Pål André Holme, Chief Physician at Oslo University Hospital and Clinical Investigator in Idogen’s study, and Dag Josefsen, who is Chief Physician and Head of Department at the Section of Cell Therapy.
Idogen develops tolerogenic cell therapies that are supposed to turn off unwanted activation of the immune system. The company’s platform technology can be adapted to a variety of diseases and conditions through small changes in the manufacturing process. The technology involves cells being taken out of the patient’s blood and treated outside the body to become tolerogenic dendritic cells. These are then returned to the patient where they are supposed to counteract the unwanted immune reaction.
The company’s leading development program, IDO 8, is aimed at patients with severe haemophilia A who have developed inhibitory antibodies to their treatment with factor VIII concentrate (FVIII). The ambition with IDO 8 is to induce tolerance to FVIII so that the important treatment once again can be given to the patient.
The study start is getting closer
Soon, the IDO 8 treatment will be tested on patients for the first time in a phase I/IIa clinical trial. The study is expected to run during 2022-2023 and will evaluate both safety and preliminary treatment efficacy. Idogen intends to conduct the study at several trial centers in Europe and has so far received approval from both the Swedish and Norwegian Medical Products Agency to initiate the study.
Pål André Holme speaks about the study and IDO 8’s potential
In Norway, the study will be conducted at Oslo University Hospital, a leading and reputable center for the treatment of seriously ill patients with haemophilia A. Clinical Investigator for the study is Pål André Holme, Chief Physician at the Department of Blood Diseases. BioStock contacted Pål André Holme to know more about the clinical study with IDO 8 and his view on the potential of Idogen’s cell therapy.
Firstly, Pål, could you tell us a bit about your professional background?
– I am a Professor and Chief Physician at the The Department of Haematology at Rikshospitalet, Oslo University Hospital, and a Professor at the Institute of Clinical Medicine at the University of Oslo. In my research work, I have mainly worked with hemostasis, i.e. blood clotting – an area that I also did my PhD in when I was 29 years old. I also have a specialisation in haematology and internal medicine.
– I have built up quite a large research group in bleeding treatment and some in thromboses (blood clots), and we have published a lot on the subject.
How did you come into contact with Idogen and what were your first thoughts when you heard about the cell therapy IDO 8?
– Our field is limited, so you hear about most of what happens there, but it was actually Idogen who contacted me. I got to read through the study protocol for the clinical phase I/IIa study with IDO 8 and thought it sounded interesting.
– What caught my interest was that it is a completely new treatment principle to create immune tolerance in patients with haemophilia A who have developed FVIII inhibitors, i.e., antibodies against the clotting protein that they lack and are treated with.
»What caught my interest was that it is a completely new treatment principle to create immune tolerance in patients with haemophilia A who have developed FVIII inhibitors. «
How extensive is the problem of inhibitory antibodies against FVIII?
– As many as 30 per cent of haemophilia A patients develop antibodies to the treatment. Patients start their FVIII treatment already as young, which means that especially children are affected by this problem.
– Antibodies to FVIII are a major and not at least costly problem, because it requires long immune tolerance induction therapy (ITI) to become tolerant to FVIII. ITI involves giving patients high doses of FVIII over a long period of time, about 3-6 months, to get the immune system to accept FVIII. The goal is for the patient not to react to FVIII and to once again be able to benefit from the treatment. However, this is only achieved in 70 per cent of cases and then a number of “problem patients” remain. It is these patients, who have no effect from ITI, that Idogen wants to help with IDO 8.
Do you think Idogen has found a solution to the problem?
– The aim with Idogen’s cell therapy it to induce long-term tolerance to FVIII by using autologous cells, i.e. the patient’s own cells. After exposing these to factor VIII molecules and treating them with Idogen’s unique process to create tolerance, they are returned to the patient. At best, the antibodies disappear completely so that the patient can again be treated with FVIII.
You were involved in Idogen’s application to the Norwegian Medicines Agency, NoMA for the clinical study with IDO 8 and will now take on the role of Clinical Investigator. Can you tell us a bit more about your role?
– I will select patients who may be suitable for the study. The patient should be at least 18 years of age, should have inhibitors against FVIII and should have failed attempts at immune tolerance induction therapy.
– I carry out a so-called baseline visit where I go through what the treatment entails and inform about the study. The patients also sign a written consent that I thoroughly go through with them.
Could you also tell us a bit more about the study design and its primary and secondary endpoints?
– The patients are only treated once with Idogen’s cell therapy and then followed up after 26 weeks. Another follow-up is made after one year. Patients will be divided into three different cohorts where three different amounts of the dendritic cells will be tested. In Norway, we will test the treatment on only one patient in the first place, which is expected to take place soon, hopefully shortly after the summer.
– Since this is a phase I/IIa study, the primary purpose will be to evaluate the safety of the treatment – we want to see if this is something we can do on a larger scale. The secondary goal is to see if the patients actually become tolerant to FVIII, i.e., that the inhibitors disappear.
How are you going to evaluate whether the patient has become tolerant or not?
– 20 weeks after the treatment with the cell therapy IDO 8, we will do a so-called provocation test where we give FVIII to the patient to see if it triggers an immune reaction. We hope that this will not happen because the goal is for the patient to have built up a tolerance to FVIII and gotten rid of their antibodies to FVIII.
– To see if the patient has become tolerant or not, you see how long the FVIII molecule stays in the body without being degraded. We have different systems for observing the amount of antibodies in the blood.
»I look forward to seeing the results from the phase I/IIa study.«
Finally, what are your hopes for the clinical study?
– Idogen’s cell therapy is a completely new type of treatment that we hope will allow many haemophilia A patients to benefit from the FVIII treatment once again, which would have very positive consequences. I look forward to seeing the results from the phase I/IIa study.
Interview with Dag Josefsen
Another key person for the clinical study with IDO 8 is Dag Josefsen who performs the so-called leukapheresis that is carried out to collect white blood cells for Idogen’s treatment. Dag Josefsen tells us more about preparations for the study in an interview with BioStock.
Dag, could you first tell us a bit about yourself and your experience in cell therapy?
– I am head of the cell therapy section at the cancer department at Oslo University Hospital. I have worked in the hospital for over 30 years and for the last 16 years in the section of cell therapy.
– I am an oncologist and have worked with cancer patients for many years. I also have a PhD in hematopoiesis and have worked a lot with stem cells. This is the reason why I work with cell therapy today. At the cell therapy section, we work with, among other things, retrieving stem cells for stem cell transplantation and T cells to produce CAR-T treatment of cancer.
How is leukapheresis performed and what is it usually used for?
– The starting point for, for example, vaccines with dendritic cells is to use cells that are naturally found in the bloodstream. In leukapheresis, the patient is connected to a machine that pulls cells out of the blood. The blood is taken out from one arm and then sent back into the other arm, which means that the patient does not have any loss of blood. The process takes 3-5 hours and then we have got out a sufficient number of cells. With the help of centrifugation, you can divide the blood into different layers, which allows you to pick out the cells that are of interest.
– Leukapheresis is used, for example, to retrieve stem cells from the blood for stem cell transplantation. When collecting dendritic cells, as with Idogen’s cell therapy, you do not need to make as much preparations as when retrieving stem cells. The cells for Idogen’s cell therapy will be taken out in much the same way as the production of CAR-T cells for the treatment of cancer.
How is the patient affected by leukapheresis? Are there any possible side effects?
– It is a simple procedure for the patient and there are no significant, long-lasting side effects. The amount of cells in the blood is not affected in the long-term, but you can see a small, temporary decrease in the level of platelets that quickly stabilizes.
»It is a simple procedure for the patient and there are no significant, long-lasting side effects.«
– However, the patient may experience some short-term side effects, such as muscle cramps and tingling in the toes and fingers. This is due to the anticoagulant medicine used to ensure that the blood does not clot. This works by binding to calcium, creating a temporary dip in calcium levels that can affect nerve and muscle processes.
What happens after leukapheresis before the cells form Idogen’s tolerogenic cell therapy and can be returned to the patient?
– You could say that we are developing the starting product for what will become Idogen’s cell therapy. The cells are then sent off to a production facility where they are prepared in several stages before they can be used for the treatment of patients. The dendritic cells are cultivated until they reach a certain degree of maturity.
With your solid knowledge in cell therapy, what would you say are the benefits of Idogen’s cell therapy?
– One of the advantages is that the cell therapy is autologous, i.e. that the patient’s own cells are used, which means that you do not have to worry about a rejection reaction occurring.
The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.
