Welcome, everyone, to the BioSoc Studio, where we today are doing this live webcast. Thank you for tuning in. We are meeting today in the context of the World Diabetes Day. It is a day to raise awareness about diabetes, Type 1 diabetes, and also the impact that this disease has on people's lives. Around 9 million people globally are living with Type 1 diabetes, and each year, roughly 300,000-500,000 people are newly diagnosed with it globally. It is a big, big medical need, and it needs to be addressed. We are here with a panel of experts that will definitely bring us new light in what's going on with the development within Type 1 diabetes. Without much further ado, I would like to introduce our panelists. From Diamyd Medical, who we are co-hosting this webcast with, we have Ulf Hannelius, CEO.
Diamyd Medical is a listed company on Nasdaq First North in Sweden and developing a GAD65-based precision therapy to preserve the body's own insulin production called Diamyd. We also have with us Professor Johnny Ludvigsson, pediatrician and Type 1 diabetes researcher, also the founder of Barnd iabetesf onden, the Children's Diabetes Fund, and principal investigator in the GAD/Diamyd trials. Welcome, Johnny. With us from the U.S., we also have Joshua Veith, who is representing Breakthrough T1D. It's a nonprofit organization that leads research strategy at global funding and funding disease-modifying trials within diabetes. Thank you for joining us from the U.S., Josh. We also have with us Professor Åke Lernmark, also a Type 1 diabetes researcher focused on genetics, HLA, and autoantibodies, central to understanding risks and prevention with the disease. Very much appreciate you taking the time to be with us today.
I would like to start by laying down some grounding basics in terms of terminology, and I'm going to address you first, Johnny. Can you just, in sort of layman's terms, tell us what does Type 1 diabetes actually mean?
Yeah, it is actually so that all of us need glucose, sugar, as fuel for the machinery. The problem is that this glucose cannot pass into the cells. It's too large. It needs an opening, and that is done by insulin. The problem is then that if you lose insulin, then the body will actually die. In Type 1 diabetes, there is a process starting. We get a civil war. The immune system, for some reason, attacks these cells producing insulin. When that starts, the autoantibodies, antibodies against these cells are seen. This is nowadays what people call stage one of the disease, but it's not clinically evident yet. Then gradually, the capacity to take up glucose decreases, and you get an intolerance with something, you know, increasing blood glucose.
Finally, there's stage three, which we call clinical diabetes, the Type 1 diabetes people think of. That is a very serious, very serious disease which cannot be cured. It cannot be prevented. You need to take insulin every day, and that should be, you know, adapted to what you eat, physical activity, infections, everything. If you are happy and it works very well, then you can continue with this for many, many years, a long life. If you, for some reason, some people develop serious complications: kidneys, eyes, heart, heart infarctions, and unfortunately, some people die too early, much too early by this. It is a very serious disease. In Sweden, for instance, it is by far the most common of all types of diseases, especially children and adolescents. You know, it is three times more common than all cancers and tumors together in Sweden.
Actually looking at them, who are at risk and why do people develop the disease? I was going to ask you, Åke, you're working with HLA genotyping. For people who have never heard the term before, what is HLA genotyping and how does HLA genes actually then affect who is at higher risk of developing the disease and how fast the disease progresses?
The HLA system is present in all people. Everybody has it. We have, during evolution, developed a way by which we can protect ourselves from virus infections, bacterial infections, parasite infections. We have learned how to transplant organs. These different mechanisms, which is human survival, is all regulated by genes coding for proteins that these proteins are able to identify fragments of virus, and the proteins are able to help the immune system to develop specific antibodies to virus. The interesting part is that these HLA genes, and they are very, very variable, as you can imagine, in people all over the world. We can use them to identify where people come from.
For example, people in Scandinavia, they have HLA genes that are very good to code for proteins that are able to protect ourselves from tuberculosis, while we are unable to protect ourselves from yellow fever. The important part is that the HLA proteins are then making some mistakes to think that GAD, for example, or insulin, are like virus proteins or virus antigens. The immune system makes a mistake to develop antibodies against ourselves. This is called autoimmunity. It's related to autoimmune diseases. In order to develop Type 1 diabetes, you inherit these HLA genes. It doesn't mean that you're going to get the disease. It means that the risk is increased to develop Type 1 diabetes if you have these particular HLA genes. They are very easy and inexpensive to find out what people have.
Thank you very much for that explanation. The insulin production decreases. C-peptide, Josh, I know this is something that you are looking into closely. What is C-peptide, and how does that show how much insulin the body can actually make?
Yes, thank you. Building on what Johnny said with the role of insulin in the body, this insulin is produced in your beta cells, which are a type of cell in the pancreas. During that process, a larger protein is broken down until you have insulin. That sort of breaking down involves different pieces of that larger molecule, one of which is C-peptide. What this means is that for every molecule of insulin your body produces, you produce one molecule of C-peptide. By measuring C-peptide, you can directly measure how much insulin your body is making.
That sounds very useful, I would say. Josh, from your perspective at Breakthrough T1D, you support a lot of research going on and so on. Why has preserving the C-peptide or endogenous insulin become such an important goal in clinical trials?
Yes, we are working very hard to make C-peptide a validated endpoint for clinical trials. The reason being is that a lot of people that enter trials at the time of diagnosis are also receiving insulin through an insulin pump. This makes it very hard, if not impossible, for us to determine how much insulin they're producing because of the insulin they're receiving from their pump. By measuring C-peptide, we are just measuring the insulin that their own body is producing. That allows us to determine whether or not a drug or therapy is preserving that and allowing them to continue their beta cells to continue to function.
All right. How would you say that, describe that? How is the field moving then from better management towards sort of more disease-modifying and preventive therapies?
Yes, it's an exciting time in the field. We've shown a number of immune-based approaches can stop the autoimmune attack that Åke spoke about and preserve beta cell function. Now we're at a point where we're looking to see why do some people respond to certain therapies and others do not. That gets us into more of a precision medicine approach. Where the field is going is learning more about the pathology of disease as it progresses and then fine-tuning our therapeutic options so they address the specific needs of a patient versus broad use of immunosuppression and other approaches.
Yeah. Precision medicine is the key here. But Ulf, when you look at the current landscape of Type 1 diabetes treatments and trials, where is Diamyd Medical positioning this GAD65-based therapy amongst other emerging disease-modifying therapies?
Yeah, thank you for that question. I can allude to what Josh already was mentioning around precision medicine. Our phase III trial, which is ongoing, is the first ever precision medicine-based phase III trial ever being done in this field. That's really been part of the learning over all the years that GAD-based therapy has been developed, that it doesn't work in all individuals, like I would say any therapeutic in any complex disease. You never work in 100%. That's been very clear for us how we've been able to adopt our development in finding the potential responders based on the HLA genetics that Åke mentioned. We are now in phase III, which is the last step before hopefully market approval and commercialization. Today we are one of three assets in phase III in the field as far as we know.
Like also Josh mentioned, there's a great momentum now ongoing in the field. If you go back 10 years back, it looked completely different, the landscape of Type 1 diabetes, the assets being developed. Now there's a lot of investments going on, a lot of awareness. We are one of three in phase III. We are the only company with a so-called antigen-based immunotherapeutic in phase III development. Again, where you specifically want to reprogram the immune system against a single component, no broad immunosuppression, but very specific treatment in a patient population that we identify based on HLA genetics. I would say, obviously, as a company, we are very well positioned in a very interesting field currently where there's a lot of momentum and phase III results coming in March next year.
We'll get right back to that in a short while. First, I would like to ask Johnny, in everyday language, if you will, what is GAD65 really, and how does Diamyd try to re-educate the immune system rather than suppress it?
Yeah, you know, GAD is one of these products from the islets of cells in pancreas. Therefore, the immune system attacks this. GAD means glutamic acid decarboxylase. It's actually an enzyme from the brain, but it's also in the blood. Together with Åke Lernmark, we discovered that 45 years ago in Linköping children. By using that, we decided 35 years ago or something like that that we should use it as people do in allergy, where if somebody is allergic against cat or birch, they give that allergen and get tolerance. We thought maybe we can do the same with an autoantigen. We started to give this in very, very small amounts under the skin. It worked. Actually, I can tell you that we could be able to show them at our lab that we got a change of the immune system.
Recently, or this year actually, the Nobel Prize was given for T-lymphocytes, where the regulatory T-lymphocytes who regulate the offices. It was something called FOXP3. We showed that we could increase FOXP3, CD25 FOXP3 positive cells, which are those regulating and decreasing the war and calming down the immune system. We create some kind of tolerance. We have a deviation of the immune system. That leads to that the war, the civil war, as I call it, the immune attack decreases and the beta cells survive. May I add to what Joshua said regarding C-peptide? You know that if you have some own insulin secretion, even with the most modern techniques, it is difficult to keep a good blood glucose balance. You tend to get high, too low blood glucose or too high blood glucose. If you have some own insulin secretion, that helps a lot.
Very much easier to balance blood glucose. You avoid serious complications, both acute and late. Extremely important.
Josh, is there anything you want to add to that?
No, no. I think Johnny summed it up beautifully. I think the key here, particularly for our approach for disease-modifying therapies, is that it's about balance, right? Type 1 diabetes is a difficult disease because not only are you trying to balance the metabolic aspect of the level between glucose and insulin, but then we're also trying to rebalance the immune system between our protective T-regs and the attacking T-cells.
We got more T-regs when we gave GAD some cue. Now we give it directly into lymph nodes, which has shown to be even more effective. There the officers sit and we present directly close GAD, and we seem to get a tolerance development in some way. We don't know exact mechanism, but it looks nice.
Looks nice. Ulf, you were alluding to your phase III study with a readout in March. What will that early readout actually tell us?
Yeah, exactly. It's kind of an interim efficacy readout that we have. In discussions with the FDA, we have gotten the green light to actually do this kind of a readout in the middle of an ongoing registration phase III trial. That's also something where we and the field are breaking new ground to really like the regulatory discussions where the FDA has been very positive in their meetings with us and others now. Specifically here, we are going to do a readout after 15 months from the start of the trial in around 170 patients. That's a bit less than more than half of the total trial. That will be 24 months follow-up.
The readout, it's being done in a pre-agreed plan together with the FDA, how we do it in a way that we are not sort of compromising the integrity of the trial. That's very important when you in a registration of big trial, you can't sort of look at all the data in the middle of the trial because you might be biased and that can destroy the whole trial then. It will be done in a way where we look at C-peptide only that was mentioned here, the marker for your own endogenous insulin production.
It will be kind of a thumbs up, thumbs down analysis where we get as the company, we will get information from a security committee that looks at the data where they say, we hope and believe it will be a thumbs up, but that is obviously we will see in March, where a thumbs up means that it is a statistically significant treatment effect on C-peptide, which means that at that interim, it looks like the treatment really is working. It is preserving your own insulin production. There the FDA has then given us the thumbs up that with good results at the interim, we can then start having the interactions with the FDA and talk about a potential accelerated approval pathway in the U.S. so that we can start going towards market already using this interim data.
We finish the full trial that then will be the complete approval of the treatment. It is a very important upcoming milestone, obviously, where we have the opportunity to look much earlier at the data in a very controlled fashion. If it looks positive, that can then lay the groundwork for an accelerated approval pathway in the U.S. It is a big thing. Most companies never come this far in the development of any therapeutic and even less so in Type 1 diabetes, which has been obviously a lot of failures over the years. Now we are close, hopefully.
Exciting times, that is. We have actually invited the viewers to ask questions through the live chat in the webcast. I will look at them in a little while and see if we have time to go through some of the questions that might have arisen. Josh, I was going to ask you, if the current immune targeted and precision approaches succeed, how might the story you tell families at diagnosis then change going forward over the next, say, 5-10 years?
I think the biggest advancement we can see in the field is the advancement of tolerizing therapies. Right now, if somebody is screened and has two autoantibodies indicating that they're progressing through Type 1 diabetes, we talk about delaying or delaying the onset or delaying diagnosis, giving them a little bit more time with producing their own insulin. The goal with moving toward immune approaches such as tolerization is to make that a lasting effect. How can we more permanently rebalance the immune system so that we're not talking about a delay, we're talking about halting? Eventually, as we develop therapies that can regenerate and support beta cells, how can we reverse and restore those individuals back to normal levels of insulin production?
Very exciting then going forward. I would like to wrap this panel discussion up by asking you each what we call a lightning round. It's just one short question for all four of you. If you had one sentence to tell someone who's living with or is at risk of developing Type 1 diabetes about the future of modifying the disease and preserving insulin production, what would you tell them? If I start with you, Åke.
Yeah, so I think one should tell everybody that the advancements made in understanding the HLA system have made it possible to pinpoint those individuals who are at risk of developing autoantibodies, for example, to GAD65. It's about 12% of the population that have the increased genetic risk for developing GAD antibodies. It's not everybody. The understanding of the HLA system, the use of the cloned, the recombinant GAD65, which we actually develop in our laboratory, is on the way to be used by the whole world researchers to try to develop means by which we can interfere with the autoimmunity and block it. Either we do primary prevention at birth or we become so clever that we can develop a medication that is putting a brake on the progression to clinical onset. In Swedish, it's called bromsmedicin.
That is exactly what the research front is trying to develop right now. I think it's very, very promising for those who have somebody affected with Type 1, but also for those who are discovered by screening to have these antibodies.
Thank you very much for that summarization. Johnny, what would your one sort of takeaway sentence to these families be?
I say, as I said yesterday evening when I gave a talk to a general population at the place in Linköping, before I get 100 years old, we will cure this disease. They are very optimistic when they look at me now. It can't be a long time.
Yeah. I mean-
I have always said that to my patients, and I still say, before I get 100 years old, we'll cure Type 1. And we will do.
I'm a gentleman, so I will refrain from asking you your age now, but I share your optimism. I would say that. Josh, what's your image then? What can we tell these families and individuals who are at risk?
I would say that we are at an exciting time and that we are going to see more advancement in the next 3-5 years years than we've seen in the last 10 - 15 years, knowing what's in the clinic and knowing what's coming. I would also urge everybody to get screened. Having a strong clinical pipeline, identifying individuals who are at risk is the most important part. The most important thing you can do to keep the field moving forward is to get screened for the Type 1 diabetes autoantibodies.
Thank you very much. Ulf, do you have any final conclusion to make? What would you like to say that installs hope?
Yeah, I agree to everything what has been said. I'm not sure if I can say something new here, but I would say that also, I mean, there are companies like us and many other companies now today that are really focused on Type 1 diabetes, and the momentum is greater than ever, which is important for the field that there's actually a lot of investments coming in now into the field. You have big pharma companies really investing in the field, which is very important. This is not only an, there's a big opportunity for families and patients to actually take part in clinical trials now. There's a lot of trials ongoing today. That's a good opportunity to take part as a patient as well in the research. I am very hopeful.
I'm obviously very biased being representing a company here, but it is truly completely different momentum in the field now, which is fantastic for us and other companies in this field because you need investments to go from research into commercialization and something that actually in the end comes and benefits the patients. We are so happy to, I mean, I must say, honored to be part of this kind of a team here, I mean, with the really key opinion leaders in the world and the largest patient organization in the world as well that are supporting us. It is humbling for us as a company. We do our best to, well, come to market and reach as many patients as possible with the technology we are developing. Thank you so much.
That's actually a perfect segue into the questions that I've received here from the viewers. I'm going to start with a very, very straightforward question, basically. If everything goes right, if everything works out in 2026, when can children under the age of 18 actually benefit from your therapy?
That's a great question and one of those questions where I have to be a politician answering. We have so far never come out with any specifics around exactly when we could be on market because that's obviously these timelines are so variable depending on different parameters, I mean, obviously pending results and then regulatory discussions and other things that affect timelines. We have no projections still publicly that we are saying, but it's in our interest and everyone's interest that this goes as fast as possible. In this world, nothing goes, I mean, it does take some time to go from results to regulatory discussions to setting up a BLA in place, getting it under review. We do our utmost, obviously, that it can go as fast as possible.
As a patient, obviously, it's good to look for opportunities as well when it comes to clinical trials that we are doing or others are doing so that you can actually try out these kinds of new technologies before they are actually approved. That's a politician answer.
Yeah, yeah. Drug development is rarely a straightforward journey. Nowhere is there. Just perhaps then at least get some sense of does your treatment then, if it sort of if it comes to market, will children under 18 be able to access it right away? Or do you need to do more studies for that?
No, children under 18, yes. The current trial, phase III trial, is from the age of 12 up to the age of 28. I mean, again, before, but at least we expect the label to be from the age of 12 and upwards. I mean, depending on the country, for example, in the U.S., I know there's a lot of off-label use, usually what's used when you use it in other, for example, ages than is officially approved around, but that's something the company and others need to agree upon. At least officially, we expect that it will be, if it's approved, it's from the age of 12 and upwards. We will do trials as well to go down in age. We have done them with subcutaneous injections.
We've had trials where we've gone down to the age of four in these healthy children at risk of autoimmunity as well. The potential is really there to go way down in age, but most likely the first indication will be from the age of 12 and upwards.
Thank you. Another question came in here is that has Diamyd asked or applied for priority voucher from the FDA to speed up the BLA if the readout is good?
Yeah, I can start by first this priority voucher. That's one of the new FDA vouchers out there that the FDA has sort of said that you can apply for. I know there's been a first round where actually Type 1 diabetes was part of it. In this case, it was Sanofi and Teplizumab or T-cell, which is approved in stage two. Now they have the new FDA voucher, which can give you a potential of getting a review of your market, your BLA in 1-3 months. It speeds up the process and you can have a lot of, so it's very positive that Type 1 diabetes actually has been part of those few first, is it maybe six or eight companies? I think thousands of companies.
Obviously, we are part of this group that are looking all the time for these different regulatory advantages. Importantly, obviously, most companies will never get this. I think thousands apply for it, but you can continue applying. Type 1 diabetes is in the mix, which I think is the most important thing. The FDA has recognized Type 1 diabetes as something important and handed out one of these vouchers already to a disease-modifying therapy. As a company, we are always very aware of all these things that are ongoing.
You're saying there is a chance.
There's always a chance.
Yeah. There's a question here addressed to Joshua. How do you think Diamyd then position themselves against other companies that you are supporting? Are Diamyd Medical unique in a sense in the way they work or their approach?
I would never presume to tell Ulf and his amazing team how to position themselves. I think that one thing the history with the Diamyd research has shown is that there is heterogeneity or differences within the T1D population. It is very likely that if somebody does not respond to one therapy, they may respond to another. I think that it is not about a one-size-fits-all approach for Type 1 diabetes. I think we have known this for a long time. I think the most important thing all companies can do is have a clear idea of who their responder population is and really target their therapy to those that are going to benefit the most.
That's great. Thank you. Another question here regarding the regulatory pathway and speeding up things. Do you intend to apply for breakthrough therapy designation? In your view, could such a designation then materially support or accelerate your regulatory path? I guess that's for you, Ulf.
Yeah, that's for me. Again, for those listeners who don't know us that well, currently we have fast-track designation, which is one of the FDA's also these expedited programs. We have that for all the stages of the disease. We also have orphan designation because we are in stage three, which is these newly diagnosed patients with remaining insulin production that's considered an orphan disease in the U.S., which also gives you certain advantages also when going to market for reimbursement opportunities and everything. Breakthrough designation is also one of the FDA's accelerated or expedited pathways, very similar to fast-track, but it gives some additional advantages. Obviously, that's also something we are looking out for as all these other designations.
In this case, what breakthrough could potentially give besides that you get even more interactions with the FDA and obviously even more potentially prioritized depending on the discussions, potentially it could give some advantages on the CMC side, which CMC means like on the manufacturing side, what is exactly required in the BLA that you send into the regulators, how much data do you need around stability, for example, and all, because it's very complex around the manufacturing. For example, that could be an area where you can get some advantages that you get a commitment from the FDA that you can maybe keep some of that stuff can be done after post-approval, for example. Again, it's definitely something we're looking out for as well as all these other potential regulatory advantages that you can receive as a company.
Speeding up things is always crucial. Speaking of speed, we are running out of time. I would like to finish up by saying thank you to all four of you for tuning in today and for sharing the advantages that are being made. We, of course, root for all of you, and we are looking forward to see what the readout says in March next year. Thank you very much, and thank you for viewing. The recording of this will be available to look at again if you would like to do that. Thank you very much.