March 2018

With a degree in medicine from the university of Copenhagen and specialized in internal medicine Steven Glazer, Chief Medical Officer of Idogen, has a broad therapeutic area experience including hematology, oncology, haemophilia, transplantation, diabetes, allergic and cardiovascular disease. In an Interview with BioStock Steven shares his insight on the company’s clinical program, his thoughts on the shifting competitive landscape within haemophilia A and his vision for Idogen as a company in the near future.

 

Steven, you have many years of international experience in clinical drug development. Could you provide a short introduction of your industry background and what you did before your current role as CMO at Idogen?

– That is correct, for the past 30 years I have worked for pharmaceutical, diagnostic and biotechnology companies in Europe and the United States and have Before joining Idogen I held the Chief Medical Officer role at Hansa Medical AB and served as Senior Vice President Development at BioInvent AB, Vice President Development at Zealand Pharma and Medical Director at Novo Nordisk.

What are the potential advantages of Idogen’s approach compared to regimens currently used to restore the response to factor VIII? 

– Immune tolerance induction (ITI) is the treatment of choice today for haemophilia A inhibitor patients; however, it requires frequent intravenous injections, in some cases for 1 year. It is associated with a success rate of about 70%. If our treatment is successful, the same or even better effect can be achieved from a few infusions of Idogen’s tolerogenic cell therapy.

 Idogen is approaching the next development phase involving patients. What is the design of your first clinical trial, and what do you expect to achieve?

– The main objective of any first in man study is an investigation of safety and tolerability. As we need to establish the optimal number of infusions and number of cells per infusion, we will design a study that allows us to investigate at least 2 dose levels with respect to number of cells per infusion in addition to multiple infusions. The patients will be very carefully monitored.

– The first study will enrol adult patients who have failed on at least one earlier protocol to induce immune tolerance. In addition to safety we will follow the effect of therapy on immunological biomarkers, Bethesda units and a test dose of factor VIII at the end of therapy. The test dose of factor VIII will reveal if the normal response to factor VIII infusion has been restored.

– From the first trial we expect to identify a dose regimen for the following studies
What are your general thoughts on the clinical development program for IDO 8, and what are the specific milestones along the way towards a potential market approval? 

– We will work in close dialogue with health authorities. I anticipate that the road to regulatory approval will require one pivotal study in adults and children, respectively. There are several ITI regimens in clinical use today that show similar outcomes. I do not believe that randomized control studies will be required for regulatory approval of our therapy if it demonstrates favourable safety and similar outcomes .It is also important to follow the long term tolerogenic effect of our therapy and benefit for the patients.

Recently we have seen an interesting development with emerging new treatments such as Roche’s Hemlibra and gene therapy. Is there still an unmet medical need in the field of haemophilia A

– Prophylactic therapy with factor VIII (factor administration in the absence of bleeding) is highly effective in reducing bleeding and long-term complications of bleeding. There are established dosing schedules with factor VIII concentrates to prevent and also to treat mild to serious and life-threatening bleeding. The effect can be monitored and adjusted accordingly.

– Swedish researchers have played an integral part in developing these guidelines and also factor VIII protocols for immune tolerance induction (ITI) in people with haemophilia, who develop inhibitors to factor VIII.

– Hemlibra was approved in 2017 for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with haemophilia A with factor VIII inhibitors. It is a bispecific factor IXa- and factor X-directed antibody. By replacing the function of natural activated factor VIII, Hemlibra promotes blood clotting.

– Hemlibra cannot be used for acute bleeding. It may be sufficient to prevent spontaneous bleeding but may not be for trauma, surgery or a more active life in which factor VIII treatment may be the treatment of choice. The long-term safety also needs to be established. Currently, immune tolerance induction is the treatment of choice in haemophilia A with inhibitors.

– Haemophilia is highly amenable to gene therapy because modest increases in factor levels can have major effects on bleeding risk. Two new studies in haemophilia A have demonstrated the feasibility of gene therapy for haemophilia. Patients with inhibitors and children were excluded from the trials. Gene therapy will not be clinically available for a number of years.

Idogen is also focusing on preventing organ transplant rejection, initially in kidney transplantation. What is the unmet medical need and what does Idogen hope to achieve in this field?

– Data provided by the Scientific Registry of Transplant Recipients (SRTR) demonstrate a 10-year overall graft survival for both living and deceased donors of approximately 55 to 60 percent.

In order to prevent chronic rejection life-long combinations of potent and unspecific immunosuppression is required which is associated with a high risk of infection and cancer.

Kidney transplantation is therefore an indication with a major unmet medical need. Idogen’s tolerogenic cell therapy is expected to reduce the need for immunosuppressive drugs and improve transplant survival.

The kidney transplantation project (IDO T) is still in an early phase, but can you briefly describe the forthcoming clinical development process, in general terms?

– It is very early; however, I expect the first trial will be carried out in living donor kidney transplantation where a family member donates a kidney.

Under very controlled circumstances and with the monitoring of biomarkers and biopsies immunosuppression will be tapered over time.

What preclinical milestones need to be fulfilled before advancing into clinical development, and what is the next imminent step from where you are today in the project? 

– We are currently designing and implementing non-clinical animal models of transplantation. We will discuss our plans with regulatory authorities when we have sufficient data.
From a development perspective: Where do you see Idogen as a company in three years from now?

– I anticipate in 3 years we will generate promising results in haemophilia and will be well into the pivotal studies. We should also have initial results in kidney transplantation.

I can also see Idogen involved in collaboration with other interested companies.