How are orphan diseases defined?
The exact definition varies depending on where you are in the world. In the EU it's defined as a prevalence of less than 1 in 2,000, which equates to about 250,000 patients across the EU.
In the US it's defined as being less than 200,000 patients, and in Japan it's a prevalence of 1 in 2,500 so it's very close to the European definition.
There is also a further category of orphan diseases, which people tend to leave out because there's very much a focus on the rare disease element, but there is also neglected diseases. These can be much more prevalent and very often are in the developing world. In the past neglected diseases have even been things like tuberculosis, for instance. today it includes such diseases as Dengue and Leprosy amongst others.
What first inspired you to work on drugs for orphan diseases?
I'll be perfectly honest, when I first started to work on drugs for orphan diseases I didn't even know what an orphan disease really was. It was quite simply in the mid-90s, I had an opportunity to join a very small private company called Orphan Europe.
It was a very small company at that time. I was the fifth or sixth employee, if I recall. They were one of the real pathfinders in the world of orphan drugs. It was from joining them and seeing with my own eyes what this involved. I found it quite amazing.
Orphan Europe was treating some very rare genetic orphan diseases. In contrast to the world of big pharma, you got very close to all the physicians and the patients themselves. I got to attend the patient group meetings, and saw the struggles of patients to get treatment which can save their lives or dramatically transform their lives.
Working on drugs for orphan diseases is incredibly inspiring. It certainly makes you get out of bed in the morning!
You have been working in the orphan disease marketplace for 26 years. How has the market changed over this period?
Immensely. One of the early things we did at Orphan Europe was to work with the EU on the orphan drug legislation that then came along and defined what is an orphan drug in Europe and what legislative framework surrounds it. This included the regulatory benefits and so on,
I saw the very first framework put in place in Europe to encourage the development of drugs for these diseases for which development wouldn't normally be economical. So that in itself was one immediate big change.
The first products then came through; the most notable early on was Genzyme's product for Pompe disease. You then started to see the involvement and the build-up of patient groups by disease and then more broadly networks of patient groups. You now have organizations such as EURORDIS and Orphanet, which provide a huge amount of information out to people who have a rare disease, which just wasn't available back then.
The other big change has been that as the marketplace has been seen to become economically viable, there has been the moving in of big pharma into the area, which has most definitely pluses and minuses in my view.
What challenges still remain and how do you think the orphan disease marketplace can be improved?
The challenges that remain are enormous. According to the Orphanet website there are currently about 70 drugs approved in Europe with an orphan designation and about another 80 or so which don't have an orphan designation but do treat what would be under an orphan disease. So there you’ve got about 150 approved products.
The vast majority of these products are for types of cancer. When you consider that there are 5,000 to 7,000 rare diseases, I think, first of all, you can see straight away that there's a huge challenge still to be met.
But in terms of how can the marketplace be improved, I feel very strongly that we must maintain the room in the healthcare system for innovation for treating these rare diseases. These drugs are inevitably very expensive, as they are developed for small populations.
Many of these therapies fulfil the European designation for advanced therapy medicinal product, including our own approach--our personalized autologous Treg type-Is for our first indication Crohn's disease, for instance, or for other diseases.
These are advanced therapy medicinal products, which include cellular therapies, into which ours falls, and gene therapies, into which many of these other approaches fall. They of course also can be very challenging to bring to the market, and so on.
So we must maintain that room for innovation, and I do have a concern about some of the products that are developed with multiple indications which have sales in excess of a billion Euros. I think they are taking a lot of money out of the system and maybe even stretching the meaning of the original legislation of why it was put in place.
I think a further thing we're going to need in the marketplace is stronger healthcare systems in the different countries, be they public or private. It's a recognition that you can't apply standard health economic assessments to these sort of products, and we all need to work together to think how we demonstrate the value of such expensive products for what are generally such small populations individually but which, overall, can be very significant.
Again, it's estimated up to 8 percent of the EU population suffer from a rare disease. As I said before, there's 5,000 to 7,000 of them, so individually it's very few but you start to bring that together, it's a lot of people.
You have recently been appointed CEO of TxCell. What is TxCell currently working on?
The main thing that we are focused on at the moment is taking our lead product, Ovasave, which is our lead personalized, antigen-specific Treg therapy (regulatory T cell therapy) into phase IIB. That is our focus.
Our strategy is to target orphan and niche indications. Sometimes you can't call them orphan. There is a difference, for instance, in the European and the US way of looking at subpopulations within a larger disease, which means some things that are orphan on one side aren't on the other.
There's about 160,000 refractory Crohn's disease patients who fail all of the treatments per year in Europe and the US alone. There's nothing to treat them at the moment. It's a very debilitating disease, and we think the approach where we take their own blood, separate their own T cells, and then generate T cells that are specific to an antigen that’s found in the area where you have Crohn's inflammation can let us treat that very specifically in a very targeted way.
I think it's a very exciting approach, and we're putting everything in place now to launch a phase IIB trial in the middle of next year.
We are also working on further indications because our technology has a number of different applications that we can look at depending on the antigen that we raise these antigen-specific T cells against.
We're looking very much at the start of next year to bring through an orphan indication as well, a second indication, which is very probably going to be the treatment of autoimmune uveitis, an eye disease.
We work very hard on our manufacturing process all the time. It's a very important part in these cell therapies. So they are the key activities that we have on-going at the moment for the company.
What made you move to TxCell?
I think what brought me here to TxCell is very much the marriage of some great cutting-edge science with a viable business model. The outgoing CEO, who's become our executive chairman (Francois Meyer), with the TxCell management team has worked on a great science that is now being turned as well into something that can actually develop products.
At the same time, it's being targeted because of this personalized aspect and because of the medical need orphan and niche indications, where I think I can also bring a lot of my experience to there. I think that's a great mix.
What do you think the future holds for tackling orphan diseases?
I think we will see the maturity of these advance therapy medicinal cell products, including our own of course. So cell therapy, gene therapy, really personalized and targeted approaches to treating these diseases.
I think what we also need to see, and I think we will see, is a very strong focus on diagnosis and biomarkers to enable early treatment and to follow treatment response for these diseases.
There are a lot of hopes. There's going to be setbacks. Very recently, and very sadly for everyone involved, was the example of the exon skipping approach to Duchenne muscular dystrophy (DMD). Everybody had enormous hopes for this treatment, but unfortunately in a trial that came out recently it didn't seem to have any effect.
So we're going to have big hopes and feel like we've got big targets. Sometimes we'll get setbacks but sometimes we're going to get great breakthroughs as well.
I think on the more healthcare side of it, I do think we're going to start to see price pressures and restricted access for some of these products if we're not careful and if we don't really make sure that we can demonstrate value for them and that the industry is seen to really be working for the good of everybody and not just to make profit out of this.
What are TxCell’s plans for the future?
We want to obviously move forward with, as I said, what we're currently working on. We want to really prove the value of our platform, so that we can really bring this personalized cellular immunotherapy to the aid of patients with really huge medical needs.
By doing that we want to create value and open up options for the future of the company itself, which can be multiple, and that's how I always like it to be.
Where can readers find more information?
About Damian Marron
Damian Marron is CEO of TxCell, the biotechnology company developing innovative, personalized cell-based immunotherapies using antigen specific regulatory T-cells (Ag-Tregs) for orphan and niche chronic inflammatory and autoimmune diseases.
Damian is a highly capable executive with 26 years specialist experience in the orphan disease marketplace. Within the orphan marketplace, he has experience in rare diseases, including SCID-ADA, Cystinosis, Acute Porphyria, Urea Cycle Disorders, Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA) and Progressive Multifocal Leukoencephalopathy (PML), and neglected and underserved medical needs, such as Multiple Sclerosis (MS) and cardiac ischemia-reperfusion injury (IRI).
Previously, he was CEO of Cytheris SA, a clinical stage biotechnology company focused on immunology through the development of IL-7 based therapeutics for indications including PML.
Prior to Cytheris, Damian was CEO of Trophos SA from 2008 to 2012. Under his tenure, Trophos spearheaded a group of major EU funded consortia of leading global experts and specialists working on a range of orphan diseases including ALS, SMA, MS and IRI. He has pushed through a Phase III trial for ALS and played a critical part in attracting EUR 34 million in funding. Damian was also instrumental in establishing and executing on a strategy for Trophos that included an innovative exclusive option acquisition agreement with Actelion, worth an initial EUR 10 million and subject to milestones worth up to EUR 195 million.
Damian has also been Executive Vice President Corporate Development at NicOx SA. During that period, he was responsible for the establishment of major collaborations with Merck and Co. Inc. and Pfizer Inc. He also participated in financing rounds for NicOx, raising in excess of EUR 175 million from stock market investors.
Previously, he held various business development and operational roles at 3M Pharmaceuticals, Orphan Europe, Rhone-Poulenc-Rorer and Glaxo.
Gene variant linked to early miscarriages identified