Latest / Lab to Lives / How To Turn Stalled Research Into Treatments For Ultra-Rare Diseases w/ Stephanie Manton

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How To Turn Stalled Research Into Treatments For Ultra-Rare Diseases w/ Stephanie Manton · Lab to Lives

• 0:09
  SPEAKER_02: Welcome to Laugh to Lives, the podcast where we ask, how do we get great ideas out of the lab and into people's lives?
• 0:20
  SPEAKER_02: Your hosts are Alexander Bou, Kiara Kianise, and Ivana Olsentai Oshida.
• 0:28
  SPEAKER_02: We are improv comedians who also work in life science.
• 0:33
  SPEAKER_02: On this show, we invite guests from the industry to give us their bold take on how we could get more health with less waste.
• 0:44
  SPEAKER_02: So whether you're developing a next generation drug, innovating in MedTech, or just curious about how healthcare moves from discovery to impact, welcome to Lab2 Lives.
• 0:59
  SPEAKER_02: Welcome to another episode of Lab to Lives.
• 1:03
  SPEAKER_02: And today in this studio with me, I have two of my co-hosts, the entirety of my co-host team.
• 1:09
  SPEAKER_02: I have Alex.
• 1:10
  SPEAKER_02: Hello.
• 1:11
  SPEAKER_02: And I have Chiara.
• 1:13
  SPEAKER_02: Hi everyone.
• 1:14
  SPEAKER_02: And with us today, we have uh Stephanie.
• 1:18
  SPEAKER_02: And I am super excited to talk to Stephanie because when I was first introduced to her as a guest, I I cried a little bit.
• 1:28
  SPEAKER_02: I hope that we can really get into the topic of how we can make a difference for patients waiting for treatment.
• 1:36
  SPEAKER_02: And Stephanie is, in my opinion, the perfect person to talk about this.
• 1:40
  SPEAKER_02: Stephanie, hello.
• 1:41
  SPEAKER_00: Hello, good to be here.
• 1:43
  SPEAKER_02: The way we usually ask our guests to introduce themselves on the show is to place themselves among the five value streams in the pharmaceutical industry.
• 1:54
  SPEAKER_02: We have the innovation stream, the manufacturing stream, the compliance stream, the commercial one and the corporate one.
• 2:02
  SPEAKER_02: Stephanie, where would you place yourself?
• 2:04
  SPEAKER_00: We like to obviously as a biotech company be in the innovation stream, but seeing we are in the ultra-rare disease space, we are forced into the compliance and the commercial stream because that is really where the issues are.
• 2:18
  SPEAKER_02: Oh, maybe a question of definition, Stephanie.
• 2:21
  SPEAKER_02: So there's rare disease and then there's ultra-rare disease.
• 2:25
  SPEAKER_02: How rare does a disease have to be to be ultra-rare?
• 2:28
  SPEAKER_00: The way you normally define it, and this is subject to which region you are operating in, but rare would be one in two thousand.
• 2:36
  SPEAKER_00: Ultra rare would then be either one in 30,000 or one in 50,000 or one in 70,000.
• 2:43
  SPEAKER_00: So people tend to kind of land on one in 50,000.
• 2:46
  SPEAKER_00: Then you have nano rare, which is one in a million, and that's really what is serviced through these end of one streams where it's one drug for one patient.
• 2:55
  SPEAKER_00: But but ultra-rare is the we like to say one in 50,000.
• 2:59
  SPEAKER_00: But that doesn't mean that if you come to the FDA and it's one in 45,000, they are not going to talk to you.
• 3:04
  SPEAKER_00: And they even have in their writing that it's subject to discussion.
• 3:07
  SPEAKER_00: And even if you're looking then at a subsection of patients that has one mutation, then the entire disease might be one in 50,000.
• 3:14
  SPEAKER_00: But that particular variant in that particular gene is one in a million.
• 3:19
  SPEAKER_00: So that makes that patient a nano rare patient with an ultra-rare disease.
• 3:23
  SPEAKER_00: So it's a longer story than just a number.
• 3:26
  SPEAKER_02: Yeah, yeah, it sure is.
• 3:27
  SPEAKER_02: And also it's important that we as an industry remember these diseases too.
• 3:33
  SPEAKER_02: It's it's not just uh the mass diseases.
• 3:35
  SPEAKER_02: A lot of a lot of uh patients also need treatment where uh there may be few people who have the innovation stream.
• 3:43
  SPEAKER_02: I I think that is a good place to be.
• 3:46
  SPEAKER_02: Even though to complete the innovation, we do need uh the compliance, and we definitely need uh to figure out how do we actually uh get the uh the medicine to the patient via the commercial stream.
• 3:58
  SPEAKER_02: All of those are necessary.
• 4:00
  SPEAKER_02: And Stephanie, I I would be curious what is your thesis about our industry?
• 4:06
  SPEAKER_02: How do we get from the lab and into getting uh medicine into the hands uh of patients?
• 4:12
  SPEAKER_00: Yes, it's a good question, and it's one that I spend most of my life thinking about these days.
• 4:18
  SPEAKER_00: We started WinCure Medicine, which is where I'm the CEO of, because we saw that there were a lot of patients that were left behind in the classic industry for developing drugs, where you need to have a very large commercial market.
• 4:40
  SPEAKER_00: It was also difficult to get funding into that space because investors are very aware of having one drug that is going for one indication where there's one big market and an exit opportunity to a big farmer.
• 4:55
  SPEAKER_00: So if you wanted to do it on smaller markets or on multiple indications, that was a little bit difficult.
• 5:02
  SPEAKER_00: We started wind cure based on my son.
• 5:06
  SPEAKER_00: I have a PhD or D-fill, as they call it, uh, from Oxford, in ultra-rare monogenic liver diseases or metabolic diseases, where liver diseases are a part of this.
• 5:19
  SPEAKER_00: And 10 years after finishing that, I gave birth to my son, who has an ultra-rare monogenic liver disease.
• 5:26
  SPEAKER_00: It happens to be one that I obviously knew.
• 5:29
  SPEAKER_00: I diagnosed him when he was uh just around 40 days old.
• 5:35
  SPEAKER_00: And then I started looking into the market of what is the standard care today, and it turned out to be something that my old supervisor had co-invented.
• 5:44
  SPEAKER_00: It was just a coincidence, but it was a coincidence after another coincidence.
• 5:48
  SPEAKER_00: And it was a symptom treatment that would take away a really bad itch called paritis, that these patients they can suffer from when they have a liver disease where bile acid builds up in the blood.
• 5:59
  SPEAKER_00: And then two weeks later, we got the report, his genetic report, and it came out saying that what he had was a splice mutation.
• 6:08
  SPEAKER_00: And I don't know how familiar you are with the technology called antisense oligonucleotides, but that is really well suited to undo issues related to splicing, and it is particularly well suited to do so in the liver.
• 6:26
  SPEAKER_00: So, with him having a splice mutation in the liver, it was an almost slam dunk for trying to make an ASO or an antisense oligonucleotide therapy for him.
• 6:37
  SPEAKER_00: I happen to also then, on another coincidence, be born into one of those families that pioneered that technology.
• 6:46
  SPEAKER_00: My father has built four companies and sold them off to Big Pharma based on that technology and has basically driven the entire field from where it was 30 years ago to where it is today.
• 6:57
  SPEAKER_00: So, with my tick my background in ultra-rare disease and my family's background in the specific modality, we started pulling our network together and made a treatment for my son that he hasn't been dosed with because in the end he turned out to be so well off that he didn't need it, luckily.
• 7:20
  SPEAKER_00: But on that journey, I met all of these parents who are also trying to do what we're doing, but they are pilots or librarians and they have to go to work still during the day and care for a child with an ultra-rare disease, and then at night try and be a drug developer and try and speak this whole new language of science that they're not used to.
• 7:41
  SPEAKER_00: And they are very often able to push this science to a certain level so they can fundraise, they go to academics, the academics will help them understand the disease and they will do animal models and they will come up with a few compounds that could serve as pretty solid candidates for going into the drug development flow.
• 8:04
  SPEAKER_00: But then they run into the capital that you need to do the toxicology studies in animals and the clinical studies in patients.
• 8:14
  SPEAKER_00: They have to find the patients, set up the entire regulatory space, which is why I said in the beginning, the compliance stream is something that we operate quite heavily.
• 8:22
  SPEAKER_00: And at the end of it, they need to get it approved and then they try and see how do we even manufacture it to get to the patients long term, because an ASO technology is something you need to dose every single year.
• 8:33
  SPEAKER_00: You need to have the infrastructure on top of needing the capital, and you simply need to have the expertise.
• 8:38
  SPEAKER_00: If you have never run a clinical trial before, or if you get one of these quotes from a company that is running the animal studies for you, it's just a long menu of things that you can say, okay, we need this, we need this, we probably don't need this.
• 8:53
  SPEAKER_00: And if you've never done it before, how are you supposed to know?
• 8:56
  SPEAKER_00: So you end up paying a lot of money for something where you might have only needed half of it.
• 9:01
  SPEAKER_00: That's why we then decided to create wind cure medicine.
• 9:06
  SPEAKER_00: Because what we do is we go in, talk to the academics, find the programs that are stalled at a certain level, and then we take them through TOX clinical trial approval and through to reimbursement access so the patients can get them.
• 9:22
  SPEAKER_00: This is a pretty heavy undertaking because there are hundreds and hundreds of these programs out there.
• 9:29
  SPEAKER_00: So for this to be feasible, we build an AI pipeline that we feed all the data that the academics bring to us into the system and evaluate which of these are most likely to succeed scientifically.
• 9:47
  SPEAKER_00: And also things such as, which is why I put us in the commercial bucket, but we do need to know is there another pharma company working on this disease?
• 9:56
  SPEAKER_00: Because there's not enough money to go around in the ultra-rare space, so we can't afford to run in parallel.
• 10:01
  SPEAKER_00: So if there's anyone else doing it, even if it is a big commercial opportunity, a big market, we're simply just not going to go for it.
• 10:08
  SPEAKER_00: There's already someone helping these patients.
• 10:09
  SPEAKER_00: We need to focus on one of the other 10,000 diseases.
• 10:12
  SPEAKER_00: So that's where we started out.
• 10:15
  SPEAKER_00: We then realized the second obstacle in this space is also once you get it through toxicology and you get a really promising lead candidate, you need to set up a trial.
• 10:26
  SPEAKER_00: And you're finding five patients for the trial or 10 patients for the trial out of 100 patients in the world.
• 10:32
  SPEAKER_00: First of all, you need to find them.
• 10:34
  SPEAKER_00: Then you need to find the ones that are interested in a trial, and they need to be at a window where you can actually treat them and get a meaningful output in the end.
• 10:45
  SPEAKER_00: They need to be homogeneous enough that you're not just selecting endpoints that point in all sorts of directions at the end.
• 10:52
  SPEAKER_00: And what happens today is that people then have to run 10 different trial sites for 10 different patients that they manage to find at the end, or maybe they never find them, or they never find enough to get statistical significance.
• 11:05
  SPEAKER_00: Or the patients that are enrolled have been talked into it in some way because there was such a heavy push from the industry or from the foundation or from anywhere else that they simply can't operate their daily life and fly off to another site and have their children dosed and then come back.
• 11:25
  SPEAKER_00: That the trial itself gets so expensive that we can't make it commercially viable.
• 11:30
  SPEAKER_00: So we created Rare Key.
• 11:32
  SPEAKER_00: And Rare Key is WinCures Patient Registry.
• 11:36
  SPEAKER_00: And what you do is you go in and you put your name, your contact details, where you're located, how old the patient is, and then you just do a data dump of whatever you have that you want to share with us.
• 11:47
  SPEAKER_00: One thing is the genetic report.
• 11:49
  SPEAKER_00: We need the genetic report because we need to know what the disease is and what the variant is.
• 11:52
  SPEAKER_00: So when we get a stalled asset in from academia, it runs through Rare Key and it says, will there be a possibility of creating a trial from the patients that have submitted to RAIRKE where we could make one trial site with five patients or maximum two trial sites with patients because their location is already shared?
• 12:11
  SPEAKER_00: Are they at an age where we presume that they will be able to receive the dosage?
• 12:18
  SPEAKER_00: And will they be able to stay on the trial because they are motivated?
• 12:23
  SPEAKER_00: And clearly they are, because if they haven't had not been motivated, they wouldn't have submitted to Rare Key.
• 12:28
  SPEAKER_00: So all of that data package then goes on to a filter into an expert review where there is a person sitting from the science department, from the compliance, from the commercial, looking at this.
• 12:40
  SPEAKER_00: And then we take the ones where we feel we can make the biggest impact.
• 12:44
  SPEAKER_02: That's two very specific solutions to two uh major problems in our industry, and both like finding the treatment that may already have been developed but just stalled because of lack of a clinical trial expertise, and then also for uh finding the patients to make it actually feasible uh to run a clinical trial.
• 13:05
  SPEAKER_02: Two very, very specific solutions uh to two of the biggest problems in our industry.
• 13:11
  SPEAKER_02: That's uh that's very impressive, Stephanie.
• 13:13
  SPEAKER_00: Thank you.
• 13:13
  SPEAKER_00: But what is also really impressive is not actually what we're doing, it's what the parents are doing in funding all of these projects and finding academics who are invested in helping these parents out and taking it through.
• 13:26
  SPEAKER_00: And I feel that a lot of people say that ultra-rare disease has to be philanthropic and it has to be nonprofit, and there's this sense of goodwill that has been extraordinary and has brought a lot of projects to a certain stage, but it also does mean that if you run it philanthropically, you cannot actually push things all the way through to clinic.
• 13:47
  SPEAKER_00: And in my opinion, it is just as bad being told that there is a molecule that could help your child, but you're 16 weeks in a rat study away from being able to dose it and you can't afford it, than being told there's nothing that can be done.
• 14:01
  SPEAKER_00: They they're told nothing can be done.
• 14:03
  SPEAKER_00: They go home, they Google, they see gene therapy, they say ASO, repurposing, they see all of these things and they say, What do you mean there's nothing that can be done?
• 14:09
  SPEAKER_00: There's lots that can be done, but nothing is being done for me.
• 14:12
  SPEAKER_00: And then they start all of this and they start fundraising and they get to a certain point.
• 14:16
  SPEAKER_00: And then it's not out of not wanting to, it's just how do you find the capital?
• 14:20
  SPEAKER_00: How do you create the infrastructure when you don't know anything about it?
• 14:24
  SPEAKER_00: And so I think if we can leverage and honor the efforts that were put into getting to a certain stage by at least pushing it over the finish line, I think this would be tremendous.
• 14:34
  SPEAKER_01: Thank you for the story, Stephanie.
• 14:36
  SPEAKER_01: Absolutely amazing that you're you're doing this and the journey, even you you've been on so far.
• 14:41
  SPEAKER_01: And uh it's it's probably quite an obvious point or question.
• 14:45
  SPEAKER_01: But listening to the story, actually, a lot of these challenges seem downstream of even a core one, which is okay, it's hard if you're not an expert in this space to run and run and fund clinical trials or to understand the regulatory positioning or this kind of thing.
• 14:59
  SPEAKER_01: Usually the way that's addressed is that we have an all whole industry that that does this.
• 15:03
  SPEAKER_01: So, what is it about these ultra-rare diseases, in in your opinion, that means that actually we're having to put this burden on parents and and academics to to learn all of this stuff rather than you know having this machinery in place that simply isn't turning its attention towards towards these issues?
• 15:24
  SPEAKER_00: It's as as you're saying, it's a good question because you're saying it yourself, this machinery.
• 15:29
  SPEAKER_00: And the moment you have something where things go in one end and come out the other end, it's very hard to tune this to all of a sudden work differently.
• 15:38
  SPEAKER_00: And if you have to really get ultra-rare disease working, you need to talk to the patients.
• 15:44
  SPEAKER_00: And I'm not saying that pharma, big pharma is not talking to the patients, but they need to talk to them in a different way.
• 15:50
  SPEAKER_00: Today we're talking about let's decentralize the trials so that everyone can participate.
• 15:56
  SPEAKER_00: That's fine.
• 15:56
  SPEAKER_00: What they do is then look at the trial site and say, what is easy for us to decentralize the blood tests we can do in people's homes?
• 16:04
  SPEAKER_00: Let's do that decentralized.
• 16:07
  SPEAKER_00: And if you ask the patient if they care about whether they have to come in for a blood test or not, they don't care about it.
• 16:12
  SPEAKER_00: They care about having to travel in for an MRI because that is simply impossible because the patient might sit in a wheelchair or might that might.
• 16:22
  SPEAKER_00: All I'm saying is what we think is possible for us to do might not be what they need us to change.
• 16:29
  SPEAKER_00: And unless we have that open and honest discussion, we will keep having the issues of patients dropping out or patients not wanting to enrol or not producing data with the level of detail that we need, because the clinical endpoints that we have set are not the ones they want to meet.
• 16:48
  SPEAKER_00: So if you if you ask them what is the most important unmet need in your disease and how can we decide endpoints around this, and obviously, sometimes science and science, you can't get everything you wish for on both sides, but let's at least try and communicate about it, then we can create a set of endpoints where we know that these parents are worried about it.
• 17:10
  SPEAKER_00: They look at it every single day.
• 17:12
  SPEAKER_00: They will see even minor changes, they will record this because it is so, so important to them rather than creating an endpoint that they didn't even realize was an issue.
• 17:23
  SPEAKER_00: And I think it's just that kind of mentality of changing the machinery.
• 17:26
  SPEAKER_00: It's it's tough.
• 17:27
  SPEAKER_03: Definitely.
• 17:28
  SPEAKER_03: What I'm hearing here is the important of having patients engaged in the conversation.
• 17:35
  SPEAKER_03: And that's the conversation that it's always on in, especially in big pharma, how do we engage patients better?
• 17:41
  SPEAKER_03: And I've and my impression is that it's quite difficult already in those diseases or quite mainstream, let's call them.
• 17:48
  SPEAKER_03: But do you see with the latest advancement, for example, in life science, we're using, and maybe I'm touching on an obvious point, but talking about AI and how we can improve the the system and then this huge machinery.
• 18:04
  SPEAKER_03: Maybe I don't know, it could be a way where we could reallocate funds because we're optimizing on certain other systems.
• 18:12
  SPEAKER_03: So we don't take so much money or resources for developing a standard clinical trial, but maybe we could reallocate those that those resources to more patient engagement and maybe more focus on understanding these diseases.
• 18:27
  SPEAKER_03: What else do you see?
• 18:28
  SPEAKER_00: That really would be lovely.
• 18:31
  SPEAKER_00: And I think the industry is moving more and more in that direction.
• 18:34
  SPEAKER_00: I can see a lot of the panel discussions or talks that I'm being asked to participate in are very much organized by farmers or by companies supporting farmers saying, how can we make patients that feel that this trial is designed for them rather than designed by us for them to participate in?
• 18:54
  SPEAKER_00: One thing that I do see is that the regular farmer space is normally designed in a way where you say, okay, where is there a big market?
• 19:04
  SPEAKER_00: Which disease is predominant?
• 19:07
  SPEAKER_00: Which gene is causing this issue?
• 19:11
  SPEAKER_00: Let's make a drug for that.
• 19:14
  SPEAKER_00: Which drug can we make for that that could alleviate some symptoms?
• 19:19
  SPEAKER_00: Let's try and find patients for it.
• 19:22
  SPEAKER_00: And then they go to foundations and they say, Do you have any patients in your registry?
• 19:26
  SPEAKER_00: And and I just would really like things to go the other way.
• 19:31
  SPEAKER_00: And that's why we created Rare Key.
• 19:33
  SPEAKER_00: It's why are we designing drugs for patients that may want them?
• 19:37
  SPEAKER_00: And then we try and push them on patients with alleviating symptoms that we think would be scientifically possible to alleviate.
• 19:47
  SPEAKER_00: When we have a huge community of patients out there that would love a treatment.
• 19:51
  SPEAKER_00: So now they're in RAIRKE.
• 19:53
  SPEAKER_00: They can say we would like a treatment.
• 19:55
  SPEAKER_00: And when we have a certain number of patients with the same disease, we can interview them and we can say, what is the largest unmet need?
• 20:04
  SPEAKER_00: Is that something that we can actually address?
• 20:07
  SPEAKER_00: If not, what is the second largest one?
• 20:10
  SPEAKER_00: Would that also make an impact?
• 20:12
  SPEAKER_00: And where should the trials be run and how for you to be able to participate in them?
• 20:17
  SPEAKER_00: And it might end up in a place where we say, okay, then that indication is not one that we can do anything about because we can't solve any of the unmet needs.
• 20:24
  SPEAKER_00: And we would need to make 10 different trials in 10 different countries, and it simply isn't commercially viable when the market is of this of this size.
• 20:32
  SPEAKER_00: But there are 10,000 diseases, and surely some of them will match a flow that will get us the whole way through.
• 20:38
  SPEAKER_02: So it's essentially building a different kind of machine.
• 20:41
  SPEAKER_02: The the farmer machine, it works the way that you described.
• 20:45
  SPEAKER_02: We we want to develop a a drug, so we look for patients that will match that drug.
• 20:50
  SPEAKER_02: Whereas the machine that you build starts with, we have these patients who are looking for treatment.
• 20:54
  SPEAKER_02: It's a different area.
• 21:02
  SPEAKER_00: It should be patients pulling on us, saying, we need these treatments, make them for us.
• 21:08
  SPEAKER_00: And instead, it's a push, which has never made any sense to me, where the industry is sitting there with drugs that we're trying to get people to buy, and if they needed them, they would buy them.
• 21:18
  SPEAKER_01: It's interesting.
• 21:18
  SPEAKER_01: It makes me think of um a phrase that we that we use quite often in our place, which is you know, to the person or the yeah, the person with a hammer, you know, everything looks like a nail.
• 21:30
  SPEAKER_01: And this makes me start to think that that maybe this is an element of of the challenge here, which is we do have this wonderful machine that we've built.
• 21:40
  SPEAKER_01: And you know, we all tend to come from very scientific places into this machine.
• 21:46
  SPEAKER_01: We're very proud of the scientific skills we have and and the way that we can develop drugs and you know to turn compounds into commercial options.
• 21:53
  SPEAKER_01: And it's sounding to me one of the elements here is that we're perhaps a little too proud of.
• 22:00
  SPEAKER_01: This machine, or a little too invested in the machine versus, well, actually, what is it that patients need?
• 22:07
  SPEAKER_01: And maybe if we change this, change the head on the hammer to this shape or that shape, then actually we can do something much better and much more effective.
• 22:15
  SPEAKER_00: I think that is true.
• 22:16
  SPEAKER_00: And I think that is true because we are proud of the machinery because it has worked.
• 22:20
  SPEAKER_00: There's been so many common diseases that we've been able to find solutions for.
• 22:25
  SPEAKER_00: And it is still working when we continue having diseases that we can keep creating markets for and therapies for in this way.
• 22:34
  SPEAKER_00: We will only be forced to run the pipeline the opposite direction the moment we run out of markets.
• 22:42
  SPEAKER_00: And I think we're getting there.
• 22:45
  SPEAKER_00: And you can see it because many of the big pharma companies are all running similar drugs, similar modalities for similar indications.
• 22:52
  SPEAKER_02: Yeah.
• 22:53
  SPEAKER_02: And it's also one of the things that I hear at conferences in the past year is uh exactly what you're saying, uh, creating the market.
• 23:01
  SPEAKER_02: So finding a drug, figuring out in which patient group does it work, and then uh approaching commercialization in the sense of creating a market for that drug.
• 23:11
  SPEAKER_02: So doing doing disease awareness, helping doctors actually diagnose uh this thing that we're trying to treat in the first place.
• 23:19
  SPEAKER_02: Now that you say this, uh it does seem kind of backwards.
• 23:22
  SPEAKER_02: Like we could also just start with the markets that already exist where patients are looking for treatment.
• 23:27
  SPEAKER_00: Such a corporate way of kind of we have something on the shelf already, how can we repurpose it?
• 23:32
  SPEAKER_00: But that is because developing it has been long and hard and expensive.
• 23:38
  SPEAKER_00: So you need to find as many markets as possible for that.
• 23:42
  SPEAKER_00: And when we make a therapy, it takes four and a half years from the patient walks in till we are able to get it to them with reimbursement so that they can basically pick it up in the pharmacy.
• 23:56
  SPEAKER_00: That costs us six and a half million euros, and that means that at the end of it, we don't need to repurpose it.
• 24:03
  SPEAKER_00: Yeah, because that that process is going to cost us the same as just starting over with another disease.
• 24:08
  SPEAKER_02: That is an insanely short and cheap process.
• 24:14
  SPEAKER_01: Exactly.
• 24:15
  SPEAKER_01: I was about to say the same thing.
• 24:16
  SPEAKER_01: Yeah, wow.
• 24:17
  SPEAKER_01: That's incredible.
• 24:18
  SPEAKER_00: We can do this because we obviously have in the company extreme expertise in that modality.
• 24:25
  SPEAKER_00: So we can look in every single step and optimize and make it as lean as possible while obviously still staying within the regulatory and safety and efficacy.
• 24:35
  SPEAKER_00: And that is the other side of that coin.
• 24:38
  SPEAKER_00: People say, okay, if you do such a lean development, are you sacrificing anything?
• 24:42
  SPEAKER_00: But for that reason, we are running everything under proper regulatory compliance.
• 24:48
  SPEAKER_00: So we are filing an IND, it's run under FDA or CTA, MHRA, EMA, any of that.
• 24:54
  SPEAKER_00: We don't have any compassionate use, we don't have anything where the doctor will take responsibility themselves and then they will run the trial.
• 25:02
  SPEAKER_00: And we just we want to make sure that there is a second pair of eyes that has absolutely no emotional or commercial incentive to push anything through that shouldn't go through.
• 25:15
  SPEAKER_02: I'm curious, Stephanie.
• 25:17
  SPEAKER_02: It does sound like you rely a lot on the expertise piece because when you run such a lean process, like there's there's not much room for training a newly graduated person into figuring out how to run a trial.
• 25:32
  SPEAKER_02: How do you recruit the experts in these fields?
• 25:35
  SPEAKER_00: We've been lucky to come with the network that we did.
• 25:39
  SPEAKER_00: And it's it's a very interesting point because people say, okay, what is your new technology or what is your new target that no one knows that we're investing into?
• 25:50
  SPEAKER_00: And what we're saying is we have no new technology, that's the whole point.
• 25:55
  SPEAKER_00: We are able to come with technology that has been tested again and again over 30 years and is already in clinic, and everybody knows the TOX profile.
• 26:05
  SPEAKER_00: We can manufacture it by pressing a button on a machine that's been around for 20 years.
• 26:09
  SPEAKER_00: If that was not the case, we could not do it this way.
• 26:12
  SPEAKER_00: And this just goes for every single, every single point.
• 26:15
  SPEAKER_00: We don't have a new technology, we don't have a new target because we are tapping into a target that is already de-risked in academia.
• 26:24
  SPEAKER_00: We're tapping into funding that has already been raised and should not go to waste by just sitting there.
• 26:31
  SPEAKER_00: And then obviously, I come from ultra-rare, my family comes from the ASO space.
• 26:36
  SPEAKER_00: That comes with an enormous network of deep, deep expertise.
• 26:41
  SPEAKER_00: We're located in headquartered in Denmark, where a lot of the anti-sense expertise is, because there's been a lot of companies here built on that.
• 26:50
  SPEAKER_00: And then we've been very, very lucky to get Andrew Rodham onto the team, and he basically knows the regulatory space inside out.
• 26:59
  SPEAKER_00: He comes from Everyone Medicines, and he's been the chief strategy officer there previously.
• 27:04
  SPEAKER_00: And he sits in on the EU Parliament discussions with drafting the Biotech Act to make sure that that then becomes optimized for ultra-rare disease as well.
• 27:12
  SPEAKER_00: Yeah, that's that's an amazing platform to stand on.
• 27:16
  SPEAKER_00: But it does mean that people say, okay, so why you?
• 27:19
  SPEAKER_00: Couldn't everyone just do this?
• 27:20
  SPEAKER_00: You know, it's not a new technology, it's not a new target.
• 27:23
  SPEAKER_00: And by all means, I hope that everybody does, because there are 10,000 diseases.
• 27:28
  SPEAKER_00: I I will be busy from now on until in three lifetimes down.
• 27:34
  SPEAKER_01: That raises a question that I had earlier when you were speaking, because obviously, in your own personal experience and the other parents that you were describing, there seems to be this real, well, there clearly is this real personal motivation to what you are all doing.
• 27:51
  SPEAKER_01: And I think that's not something that we usually necessarily think about or talk about in in business, right?
• 27:58
  SPEAKER_01: Business is set up to be this kind of, I'm gonna say rationalist, emotion-free zone.
• 28:04
  SPEAKER_01: But do you feel there's an advantage for you folks coming from this?
• 28:10
  SPEAKER_01: No, we are personally invested here and we are determined to get something done that works for the people that we care about.
• 28:18
  SPEAKER_00: Absolutely.
• 28:19
  SPEAKER_00: I like to say I believe that I would be as invested if I had not had my son, just because I get extremely invested in what I care about in general.
• 28:28
  SPEAKER_00: I do see it as both an advantage and a disadvantage because you have people who are so invested that they are likely to, for example, stay on the trials at the same time.
• 28:39
  SPEAKER_00: If you then have to turn someone away because they don't fit into the trial, it is such a small community that unless you really make sure you balance out how you describe to that patient why they cannot participate in that trial, knowing it's life or death for that patient, that might come back to you in a less ideal way.
• 29:00
  SPEAKER_00: And that's also why people say it has to be philanthropic, it has to be nonprofit.
• 29:04
  SPEAKER_00: You're looking the patient straight in the eye.
• 29:06
  SPEAKER_00: How can you even talk about a business model?
• 29:07
  SPEAKER_00: And we are talking about a business model because if we don't, the drug will never get to the patient.
• 29:12
  SPEAKER_00: That that's what we've seen the last six years, where it's been running on a nonprofit model.
• 29:16
  SPEAKER_03: But that's also often when we talk about nonprofit, it's all it's often the myth that nonprofits make no money.
• 29:22
  SPEAKER_03: But it's actually even to work, it still is an organization, still needs to rely on KPIs, outcomes.
• 29:29
  SPEAKER_03: And I cannot stop thinking about the fact what you said about this is such an important field, people suffering and suffering mostly alone because it's ultra rare.
• 29:41
  SPEAKER_03: So, yeah, we tend to put them aside and we hope that philanthropists will help them.
• 29:46
  SPEAKER_03: But I don't know, you guys, I became a scientist because I was volunteering with children in hospitals, and that was the way for me to help people.
• 29:54
  SPEAKER_03: It's been super unfair that we are sourcing such meaningful work to nonprofits and also kind of being hands-off.
• 30:01
  SPEAKER_03: Might be a bit of strong take, but I still think that that could be this amazing collaboration.
• 30:06
  SPEAKER_03: And also, you mentioned academia has been doing a lot of fundraising, a lot of research.
• 30:11
  SPEAKER_03: The technology works because of the academic work that I've been doing.
• 30:16
  SPEAKER_03: And that's a clear example of how actually pharma and academia could work more together, just in general, in many other areas, to bring the solutions to patients faster, no matter what the disease they're affected by.
• 30:31
  SPEAKER_03: So I get a bit warm about this when I hear it should be just nonprofit and also considering nonprofit like no money air space.
• 30:42
  SPEAKER_00: That is certainly true.
• 30:44
  SPEAKER_00: And there is kind of a sense of industry not wanting to work with academia directly because there are a lot of different interests, academia needs to publish, industry needs to not publish.
• 30:58
  SPEAKER_00: So, you know, it's yeah, and it's tough sometimes.
• 31:01
  SPEAKER_03: That's super sad because I think no matter the machine we're talking about, we should all be motivated by one outcome.
• 31:08
  SPEAKER_03: We should all agree that what we want is that patients get solutions, patients get treatment, and we're solving diseases.
• 31:14
  SPEAKER_03: It shouldn't be the incentive to publish in academia, it shouldn't, in my opinion, of course, it shouldn't be not to publish.
• 31:21
  SPEAKER_03: So I guess maybe when we were talking about remain restructuring the machinery, maybe also talk, uh thinking differently about incentives, what drives us all to work in this space, because I think that this one space here, and then we're complicating things so much by putting ourselves in boxes and with different incentives.
• 31:42
  SPEAKER_00: It is very true.
• 31:43
  SPEAKER_00: I will also say that what I sometimes hear is a lot of these kind of discussions about what should be changing, what we should do differently, you know, we should share data more and we should listen more to patients.
• 31:57
  SPEAKER_00: And some of these things are actually working against our own interests.
• 32:02
  SPEAKER_00: Because if we want to be able to push ultra-rare disease out of philanthropy, out of nonprofit, we cannot share data.
• 32:11
  SPEAKER_00: Because sharing data is great for that space.
• 32:14
  SPEAKER_00: If we want to move it to a commercial model, it doesn't work if we are then, as a small company who is trying to create a commercial opportunity out of not a very large market, also has to share all the data, which is the only thing we have that makes us stand out and investable.
• 32:31
  SPEAKER_00: So I'm a little bit worried sometimes about the goodwill that comes behind all of these incentives.
• 32:38
  SPEAKER_02: It also sounds like it almost comes with like a moral judgment of some sort when some people may argue that it should be philanthropy, as though uh having a solid business model is not uh the most effective way to actually solve many of the problems that we as humanity face.
• 32:56
  SPEAKER_00: That's because people think that making money is something you're making because you want to make money.
• 33:02
  SPEAKER_00: We're not making money because we want to make money, we're making money because it's the only way we can get the treatments through to the patients, at least in our model.
• 33:10
  SPEAKER_00: There are other ways, but for us that's the way.
• 33:12
  SPEAKER_00: And the money that we make will go into making more therapies.
• 33:15
  SPEAKER_00: So it's not the goal, it's it's just the means, it's what we need.
• 33:21
  SPEAKER_01: I've got to say, I had a bit of reaction to this point earlier about, well, you know, this is something that clearly involves emotions or feelings.
• 33:29
  SPEAKER_01: So it doesn't belong in the in the business space, it belongs in the in the philanthropy space, right?
• 33:35
  SPEAKER_01: But I think actually what we also heard from you is that you're getting drugs through to market in what, a third, a quarter of the time of other people and with much less cost.
• 33:47
  SPEAKER_01: So actually, maybe there's an argument there for well, the rest of the industry should become more, you know, personal motivation led, because that can lead to clearly a better way of doing things.
• 33:58
  SPEAKER_00: At least people should make sure that they focus on what they are very good at.
• 34:04
  SPEAKER_00: Foundations are very good at getting patients in, talking to them, making them feel heard, understood, collecting natural history data, being able to support trials and make the patients feel that they have a safe space.
• 34:17
  SPEAKER_00: Academia is very good at doing the mode of action mapping, really understanding what this disease is all about, getting all the way through to kind of a proof of concept, and they can publish that if they remember to take out IP.
• 34:29
  SPEAKER_00: I'm saying the shout out to every single academic, take out IP, because otherwise I can't go here.
• 34:33
  SPEAKER_01: Yeah, please.
• 34:34
  SPEAKER_00: Um the struggle that they then run into is they are not always allowed to file IP because there is a limited amount of money that a university can spend on IP and they need to spend it on the pieces of IP that they think are most likely to get licensed.
• 34:51
  SPEAKER_00: And that is not the one where there are 100 patients, it's the one where there are a thousand patients or more.
• 34:55
  SPEAKER_00: We try and find some of these programs just before they're published so that we can tell them, hey, just file IP before you publish.
• 35:03
  SPEAKER_00: Then industry can come in and do the rest of the package.
• 35:06
  SPEAKER_00: And I just I think there is a space for philanthropy, there is a space for nonprofit, there is a space for grant funding and all of that in the earlier part of the pipeline.
• 35:15
  SPEAKER_00: But there's just no way that we should set up a flow where anyone should do something they're not good at.
• 35:22
  SPEAKER_00: It's also not in the patient's interests.
• 35:24
  unknown: Yeah.
• 35:25
  SPEAKER_02: What I really am inspired by is how much you have simplified the model, like the drug development model, how much focus you have created on the outcome.
• 35:35
  SPEAKER_02: The purpose is to get this treatment out to these patients.
• 35:39
  SPEAKER_02: And just like thinking of pharmaceutical companies that I have worked for, like it is never that simple.
• 35:44
  SPEAKER_02: There's like there's all this other stuff that occurs that probably like are more nice to have than just getting uh the treatment out there.
• 35:55
  SPEAKER_02: And perhaps like it is possible because you have such a clear patient population that you know is waiting for this treatment.
• 36:02
  SPEAKER_02: You you cannot afford the noise or the distraction.
• 36:05
  SPEAKER_02: And it's very clear to decide is this actually going to help us get this treatment out, or is it just a nice to have?
• 36:12
  SPEAKER_02: Like I'm uh my mind is boggled right now.
• 36:14
  SPEAKER_02: How could how could we simplify the the machine to the actual thing we're trying to do?
• 36:21
  SPEAKER_00: I I will say we did start in a very different place.
• 36:24
  SPEAKER_00: We started out thinking we would help all of these NF1 patients that walked into the office saying, I have already collected all the money, make a drink, a drug just for me, and take it through compassionate use.
• 36:34
  SPEAKER_00: So, you know, we did start at the nano-rare end of things.
• 36:37
  SPEAKER_00: And then the more informed we got, and the more we went to conferences and met the patients and saw the problems and read the literature, the more I just realized that the issue is much broader and it needs a revamp of the entire pipeline.
• 36:55
  SPEAKER_01: I was just looking up there, and there's a really great book that's that's certainly been very informative for me.
• 37:00
  SPEAKER_01: And I think touches on this.
• 37:01
  SPEAKER_01: It's called For Whom Will We Exist by a guy, I think he's sweet called Hans Plum.
• 37:07
  SPEAKER_01: But it's it's all about this, and actually it's about the fact that well, business's purpose isn't actually in a lot of ways to make money, that's kind of like a side effect.
• 37:18
  SPEAKER_01: What what really the focus of any successful business is is is on delivering value to a particular customer group, in our case, patient group or stakeholder group.
• 37:30
  SPEAKER_01: And I mean, my personal belief and what I really like about your story, Stephanie, is actually if you if you can align that, if you can decide, well, this is the value that I'm delivering, and I'm going to be laser focused on building a machine, a tool, a hammer, whatever that delivers that, then I can trust a successful business follows.
• 37:49
  SPEAKER_01: But I think that's very much the opposite way around to which we're trained to to kind of think of this stuff.
• 37:54
  SPEAKER_01: But is that does that also resonate with you?
• 37:56
  SPEAKER_01: Is that how you see things?
• 37:57
  SPEAKER_00: Or absolutely.
• 37:58
  SPEAKER_00: I think we are only successful because of the laser focus.
• 38:01
  SPEAKER_00: And I will say, you know, as much as we're talking about involving patients and all that, I'm I'm not a mother Teresa.
• 38:06
  SPEAKER_00: Like I have no intention to be.
• 38:08
  SPEAKER_00: I still operate the business side of things, and I need to build a pipeline that will bring us a portfolio return at the end of it that investors are interested in.
• 38:17
  SPEAKER_00: But that also does require that extreme kind of laser focus and really being able to say, okay, what are the milestones that we need to meet and by when?
• 38:26
  SPEAKER_01: No, and I think the other nice piece of that that's come up a little bit is the power of a unified goal and particularly a unified value delivery that in terms of aligning all of these different actors, because we already talked about put people who are good at the role in that particular role.
• 38:44
  SPEAKER_01: But it sounds like what you're also doing is using the overall goal to set the incentives of all of those people.
• 38:51
  SPEAKER_01: So the message to academics is you know, great that you're providing this data support, but make sure you get the IP done before you patent.
• 38:58
  SPEAKER_01: And investors, look, we know this isn't the usual case, but there is still a business here.
• 39:03
  SPEAKER_01: And parents, you know, we we know that you you really want your your uh children involved in this trial, but just know that for the trials to succeed, there's certain things we also need.
• 39:15
  SPEAKER_01: And so you've it really feels like you've got this this core goal as a focusing element that everything else is is sort of orienting around.
• 39:24
  SPEAKER_00: A hundred percent.
• 39:25
  SPEAKER_00: And it's never easy to be a first mover.
• 39:27
  SPEAKER_00: There is a lot of education of investors, of academics, of patients, you know, RAICE.
• 39:34
  SPEAKER_00: The the entire pipeline only works if patients submit to RAIC.
• 39:38
  SPEAKER_00: So if no one submits, I I like to think then there's no need, but I know that's not true.
• 39:44
  SPEAKER_00: But it would be great if that was the case.
• 39:47
  SPEAKER_00: But I just I have this dream of just whenever a genetic report is created, you ask the patient, would you be interested in a therapy being developed for you?
• 39:58
  SPEAKER_00: And if you are, submit to Reiki.
• 40:01
  SPEAKER_00: It's not a promise.
• 40:02
  SPEAKER_00: We can't promise everyone a therapy, but the more patients are in there, the more able we are to map the market, find the patients, find the need, create a trial and do all of that upfront so that we can see what actually works and what might work down the line.
• 40:18
  SPEAKER_00: That's the other thing.
• 40:19
  SPEAKER_00: And we start obviously with the diseases that have 200 patients, and eventually we will run out of those.
• 40:25
  SPEAKER_00: And then we will take the ones that have 100, and then we run out of those, and then we'll make it down to the end of ones.
• 40:32
  SPEAKER_01: We've talked a lot so far on the industry side.
• 40:36
  SPEAKER_01: How do things look on?
• 40:38
  SPEAKER_01: I'm gonna call it the hospital, governmental, particularly reimbursement side, because uh it feels like this also has two two ends.
• 40:47
  SPEAKER_01: You've got to develop the solutions for these devices in in an affordable way, but then you also need to be reimbursed for them in a way that works.
• 40:55
  SPEAKER_01: How does that side of things look currently in this in this?
• 40:58
  SPEAKER_00: That's a great, great question.
• 41:01
  SPEAKER_00: There are so many incentives right now with a plausible mechanism with this new ultra-rare or rare uh framework in MHRA in the UK, with the Biotech Act coming out in the EU, that will really make it a lot easier to run a trial in ultra-rare disease.
• 41:19
  SPEAKER_00: So instead of having a multi-armed trial where you have a placebo and a treatment, and then you compare those, you instead compare the patient to their own baseline.
• 41:31
  SPEAKER_00: So you measure them against natural history and you say, okay, we've tested these biomarkers in blood for a year every month, and this is your line, and now we start treating you.
• 41:42
  SPEAKER_00: Does the line go up or down or nothing?
• 41:45
  SPEAKER_00: So you don't have to have as many patients, which means the trial itself gets cheaper, which means in turn we can actually develop therapies for these spaces.
• 41:56
  SPEAKER_00: And we also don't need to find a lot of patients compared to what you would have to if you had to have a placebo arm and a double-blinded extra trial.
• 42:05
  SPEAKER_00: And that is something that they're now allowing in a lot of countries or are about to allow.
• 42:10
  SPEAKER_00: The reimbursement side is really the next big hurdle.
• 42:15
  SPEAKER_00: Our suggestion has been to try and come up with a way of saying to developers, if you are able to meet the following clinical endpoints, you will get reimbursement.
• 42:27
  SPEAKER_00: Then it's a conversation the whole way through.
• 42:30
  SPEAKER_00: We set the trial up front.
• 42:32
  SPEAKER_00: Of course, that will take some commitment and some capital that you would not necessarily otherwise have committed at that earlier stage, but it makes your case investable because they know that there is a market at the end.
• 42:46
  SPEAKER_00: And this is something that I like to advocate for, and that I think in the UK, they're a little bit more advanced on the reimbursement part of it.
• 42:55
  SPEAKER_00: The other thing is is there a way that we can take a regulatory approval from, let's say, the UK, where that part has evolved, and then take it to Australia and get reimbursement in Australia where that part has evolved, and then take that reimbursement and market value and take that back to the UK and say, see, in Australia, they had now allowed this price, you should match it.
• 43:22
  SPEAKER_00: And then hope that eventually they will realize, okay, this is actually the general value for these therapies.
• 43:28
  SPEAKER_00: Maybe we should reimburse them.
• 43:30
  SPEAKER_00: In the EU, there are 27 member states.
• 43:32
  SPEAKER_00: And I keep telling people we can't have a company with 12 scientists developing drugs and then 27 lawyers because we need to have one for each member state.
• 43:41
  SPEAKER_00: And what will happen is medical tourism.
• 43:44
  SPEAKER_00: Because we were thinking of actually putting into our pipeline this AI flow when they map the patients and say, okay, there is one patient in the UK, one in France, and one in Poland.
• 43:56
  SPEAKER_00: Where to look for reimbursement?
• 43:58
  SPEAKER_00: Why should you favor one over and No, let's look for reimbursement in Germany because that's right in the middle, and everyone can travel to it.
• 44:05
  SPEAKER_00: Yeah.
• 44:06
  SPEAKER_00: Even if there are no patients in Germany.
• 44:08
  SPEAKER_02: That is a model I have seen for uh other companies offering even support to traveling to a different country to get access to a drug.
• 44:16
  SPEAKER_02: Interesting evolution of our space.
• 44:18
  SPEAKER_00: Yeah, and it's they they say, okay, but isn't it really unfair to ask patients to travel for medicine?
• 44:25
  SPEAKER_00: But I can tell you 85% of patients with ultra-rare diseases relocate anyway the moment they get the diagnosis because they want to be closer to a hospital or a specialist or some other type of care.
• 44:36
  SPEAKER_00: We did it too.
• 44:37
  SPEAKER_00: We moved to France for a specific person.
• 44:39
  SPEAKER_03: I'm having I'm having this uh weird thought of you know, there there's now this trend of building villages around uh specific uh, you know, needs.
• 44:49
  SPEAKER_03: I was wondering, I mean, it just came to my mind it might be silly, but what about having like a village for these people to get, you know, so everything would be in one space.
• 44:58
  SPEAKER_03: Yeah.
• 44:58
  SPEAKER_00: You know what I wish.
• 45:00
  SPEAKER_00: I spoke to my father 20 years ago when NTSense came out.
• 45:05
  SPEAKER_00: And I remember us having this conversation about one day there will be an island, and it will be a medical island, and people will travel there, yeah, and we will put the sequence that they need into a little machine.
• 45:17
  SPEAKER_00: It will come out, we'll dose them and off they go.
• 45:20
  SPEAKER_01: Well, I think also quite a lot of the time, good innovations, particularly in ways of doing things, tend to come from these highly stressed edges, right?
• 45:30
  SPEAKER_01: Where you're really trying to do something difficult.
• 45:33
  SPEAKER_01: And actually, it's it's not that you wouldn't like to do what everyone else is doing.
• 45:37
  SPEAKER_01: It's just, you know, you can't, there's a constraint in the way.
• 45:40
  SPEAKER_01: You can't spend 20 years and a billion sort of bringing these things through to market.
• 45:46
  SPEAKER_01: And the reason I say that is that it already sounds like some of these changes that are being made at the edges in this space actually have utility if looped back into the full healthcare system.
• 45:59
  SPEAKER_01: And particularly your point about trials, you know, RCT is still the gold standard, but the ability to reliably reduce trial size by comparing people to baseline in some cases rather than a control group, I imagine Ivana can tell me much more about this as well, would have a huge impact on all of these other disease areas where we're really struggling to bring drug products through.
• 46:21
  SPEAKER_00: It is something that they're talking about that you can use across the line.
• 46:26
  SPEAKER_00: And it's specifically relevant for the diseases where it's actually life or death, because how are you going to choose which one gets the placebo?
• 46:36
  SPEAKER_00: It's just, I mean, I'm not making the choice.
• 46:39
  SPEAKER_02: And also for patients, this is one of the uh key areas where people do hesitate to participate in clinical research.
• 46:46
  SPEAKER_02: Is am I really going to waste a year of my life not receiving active treatment?
• 46:50
  SPEAKER_02: And it's a valid concern.
• 46:52
  SPEAKER_00: It's not even a concern, it's just unethical.
• 46:55
  SPEAKER_00: Or, you know, they they're asking patients to come in for a 24-hour brain infusion where they are in induced coma, only for everyone subsequently to find out that all of that was a placebo to see if the needle itself created any scar tissue.
• 47:14
  SPEAKER_01: Yeah.
• 47:15
  SPEAKER_00: Guys.
• 47:16
  SPEAKER_01: No, it's a huge impact on people's lives.
• 47:18
  SPEAKER_01: And uh yeah, the the cost benefit seems not really worth it in those cases, right?
• 47:23
  SPEAKER_01: Yeah, I'm I'm also in this uh interested in this idea.
• 47:25
  SPEAKER_01: I mean, pharma has right now a or is getting towards a bit of a reimbursement challenge, right?
• 47:31
  SPEAKER_01: The drugs are getting more expensive, but it's getting harder and harder to to make money on them.
• 47:36
  SPEAKER_01: And I liked your idea about it reminded me of post-market surveillance, right?
• 47:40
  SPEAKER_01: We're we're getting used to this now in terms of clinical data.
• 47:43
  SPEAKER_01: So our phase four, understanding what things do in real life and using that to to better justify our clinical efficacy and safety.
• 47:52
  SPEAKER_01: But yeah, why not extend that to reimbursement as well?
• 47:56
  SPEAKER_01: As we understand more the impact of a drug in real life when used in patient populations, you know, maybe even segmented by certain genetic factors or whatever, then that seems like another way to kind of optimize this and optimize health system costs as well.
• 48:11
  SPEAKER_00: People are actually already doing this, people are already doing this from gene therapies because that comes in at a price point that no budget that is a running budget from the government can afford to give one patient.
• 48:25
  SPEAKER_00: So they are talking about saying, if you meet this milestone this year, we will pay you this.
• 48:33
  SPEAKER_00: If you then meet this milestone the following year, we'll pay you this up until we have reimbursed you the full amount.
• 48:38
  SPEAKER_00: And I think that's one of the reasons why it was really important for us to make a lean structure in terms of how much it costs to develop it, because people say, okay, ultra-rare disease space, it's not a problem.
• 48:47
  SPEAKER_00: We can make it commercially viable.
• 48:49
  SPEAKER_00: We just increase the price of the medicine.
• 48:51
  SPEAKER_00: Because that's what they have done for a lot of other things.
• 48:54
  SPEAKER_00: When you kind of have smaller markets, you have higher prices to make it more viable.
• 48:58
  SPEAKER_00: But there is a cap to how much we can pay.
• 49:02
  SPEAKER_00: And from our side, there's also a cap to how much we want to charge.
• 49:05
  SPEAKER_00: And that is probably the only place where I'll say my rare diseased mother head comes on.
• 49:11
  SPEAKER_00: I feel that it's unfair for families that already have a lot of costs associated with having a child that's sick and needs a lot of different tools to operate, to also then have to pay more for a therapy.
• 49:23
  SPEAKER_00: You're already being punished enough.
• 49:25
  SPEAKER_00: There's no one you can talk to about your disease, it's already super lonely.
• 49:28
  SPEAKER_00: You already have to buy all of these things and get full-time standard care, and it's affecting the entire family.
• 49:34
  SPEAKER_00: And then you also get this extremely high price for your drug just because you happen to be one in a million.
• 49:42
  SPEAKER_00: We keep our prices completely aligned with those of rare disease.
• 49:45
  SPEAKER_02: That that makes a whole lot of sense.
• 49:47
  SPEAKER_02: And also just from an ethical perspective, how lean could the rest of Pharma be?
• 49:53
  SPEAKER_02: What is how could the machine actually look like if we were as laser focused as Stephanie describes Windure being?
• 50:01
  SPEAKER_02: Oh my goodness, would I love to see this uh thought experiments uh lived out completely?
• 50:06
  SPEAKER_02: And with that, I will start leading us towards the last part of our episode today, which is our game show round.
• 50:16
  SPEAKER_02: Chiara, Stephanie, Alex, I will have you uh guessing three different uh FDA abbreviations.
• 50:24
  SPEAKER_02: Yes, and there are essentially no sticks in in this quiz, just some pride.
• 50:29
  SPEAKER_01: Pride like yeah, unlike the entire rest of the conversation.
• 50:34
  SPEAKER_01: This is our jarring shift in tone stage of the uh yes.
• 50:41
  SPEAKER_02: Then my first uh question to you is what is Elsa E L S A?
• 50:49
  SPEAKER_02: Is it a very cold person?
• 50:51
  SPEAKER_02: Is it an elderly Swedish woman working for the FDA?
• 50:55
  SPEAKER_02: Or is it the FDA's enterprise AI platform designed to improve reviewer productivity?
• 51:03
  SPEAKER_01: I'm I'm happy to jump on jump on that one first.
• 51:06
  SPEAKER_01: I as soon as you said Elsa, I was like, ah, I've heard this somewhere, I've heard this somewhere.
• 51:12
  SPEAKER_01: And yeah, I've got a little tickle in my mind that maybe they have started to build this AI system to help navigate and inform on the on the process.
• 51:23
  SPEAKER_01: So I'm gonna take a chance and say that.
• 51:25
  SPEAKER_03: Yeah, I would uh say the same.
• 51:28
  SPEAKER_03: Uh also because I wouldn't imagine that they would just name what were the other two, like the very cool woman, and there's also like quiz Swedish woman.
• 51:39
  SPEAKER_03: So there's like quiz psychology here.
• 51:42
  SPEAKER_01: I mean, also all these AI systems, and I'm gonna be critical here.
• 51:46
  SPEAKER_01: All of these ice AI systems always have women's names, which feels a little bit like come on, it's 2026 people.
• 51:54
  SPEAKER_00: Oh, isn't it storms?
• 51:57
  SPEAKER_00: Aren't storms also uh always called something female?
• 52:01
  SPEAKER_01: I think storms are I think it depends on the country.
• 52:03
  SPEAKER_01: I think storms are mixed.
• 52:04
  SPEAKER_01: But um, I'm not sure on the personal support system's always being named after women.
• 52:08
  SPEAKER_01: I'm not sure is best approach anymore.
• 52:13
  SPEAKER_01: But there we go, that's a personal criticism I have for the AI industry.
• 52:16
  SPEAKER_01: Mark Zuckerberg, if you're listening, uh email me, I'll detail my concerns.
• 52:25
  SPEAKER_02: Well, I I can perhaps give one more clue, and that is ELSA is friends with Halo, A L O, which is a modernization initiative that aims to consolidate legacy systems across the FDA.
• 52:42
  SPEAKER_02: And ELTA is indeed their AI platform to uh improve reviewer productivity.
• 52:48
  SPEAKER_00: And people wonder why you say that regulatory is a boring field.
• 52:58
  SPEAKER_00: My husband is not a scientist, and he uh he used to laugh at the titles of my papers.
• 53:03
  SPEAKER_00: He's like rolling off the tongue is the longest and half of it abbreviations.
• 53:09
  SPEAKER_01: Yeah, no, we love the abbreviations in the regulatory space, definitely.
• 53:12
  SPEAKER_02: Next question: What is uh the AIMS?
• 53:16
  SPEAKER_02: A E-M S Ames Is it an elderly Scottish man working for the FDA?
• 53:22
  SPEAKER_02: Is it a type of sandwich?
• 53:24
  SPEAKER_02: Or is it the adverse event monitoring system for safety surveillance?
• 53:29
  SPEAKER_02: I am not uh giving you any uh any help here.
• 53:34
  SPEAKER_00: I was so I would go for the sandwich, it's definitely I was thinking it because but isn't that called Yams?
• 53:42
  SPEAKER_00: That's like the South South American or South uh so cute.
• 53:50
  SPEAKER_01: Yeah, well, I mean, obviously, adverse event monitoring system makes the most sense.
• 53:54
  SPEAKER_01: I'm quite taken with the idea of a friendly Scottish chap called Ames working in the FDA.
• 54:03
  SPEAKER_01: And I know sometimes some answers have more than more, some questions have more than one answer.
• 54:07
  SPEAKER_01: So I'm gonna say both A and C.
• 54:12
  SPEAKER_01: I hope you're also listening to the podcast.
• 54:15
  SPEAKER_01: Please also send me an email.
• 54:16
  SPEAKER_02: Well, I do hope we hear back from Ames, who is a nice Scottish chap working for the FDA, and that he's happy and Ames as he's listening to this episode.
• 54:28
  SPEAKER_02: I would love yeah, would love to hear from his mom why that name makes sense.
• 54:35
  SPEAKER_02: And also I want to hear his thoughts about this adverse event monitoring system uh and how he feels it's working out for them.
• 54:42
  SPEAKER_02: Last question.
• 54:43
  SPEAKER_02: Speaking of things that are hard to pronounce, what is the RTCT?
• 54:50
  SPEAKER_02: Is it a kind of robot?
• 54:52
  SPEAKER_02: Is it a new data standard?
• 54:54
  SPEAKER_02: Or is it a pilot program testing real-time clinical trial data submission?
• 54:59
  SPEAKER_00: I was in a two-day meeting with FDA last week in Washington, and this was being said a lot.
• 55:07
  SPEAKER_00: And I was sitting in this meeting thinking, I'm not sure I was the right one for WinCure to send because I don't know what that stands for.
• 55:15
  SPEAKER_00: So here I am, being told by you guys.
• 55:18
  SPEAKER_00: Let me know.
• 55:19
  SPEAKER_01: Is there not a secret fourth option?
• 55:21
  SPEAKER_01: Like, because they're doing a new Star Wars film, right?
• 55:24
  SPEAKER_01: RTCT, is that not the droid type TV Star Wars?
• 55:30
  SPEAKER_01: Maybe I made that one up.
• 55:32
  SPEAKER_00: The song, is there not like a RTCT S V Play?
• 55:40
  SPEAKER_01: RTCTCD.
• 55:42
  SPEAKER_01: Yeah.
• 55:43
  SPEAKER_01: Don't know what it means to me.
• 55:45
  SPEAKER_01: Absolutely not.
• 55:46
  SPEAKER_01: It's a completely impenetrable acronym.
• 55:49
  SPEAKER_02: I really do hope that this is something that takes off because I hope that we will be able to monitor and uh get feedback on real-time clinical trial data submissions.
• 55:59
  SPEAKER_02: That would be so cool if they actually pulled off RTCT.
• 56:03
  SPEAKER_01: Any any listeners are gonna have to go through so much attainment to get into any info here.
• 56:10
  SPEAKER_02: Well, that does conclude this episode.
• 56:13
  SPEAKER_02: I am curious to hear from both Stephanie and Alex and Chiara.
• 56:17
  SPEAKER_02: What are your main takeaways from our conversation today?
• 56:20
  SPEAKER_02: What will you be thinking about tomorrow in the shower or as you drink your coffee or tea in the morning?
• 56:27
  SPEAKER_03: Yeah.
• 56:28
  SPEAKER_03: My my takeaway, I think, is that you, Stephanie and your company, what you're doing is the real example of how we when there is a will, there is a way.
• 56:38
  SPEAKER_03: And I wish for our beautifully functioning machine that we have at the moment to be able to catch up with all those disease and all those patients, there are still need.
• 56:52
  SPEAKER_01: No, and I think a similar thing for me, proof if it was ever needed that what you can do if you start from passion and delivering value and motivation and not simply, well, you know, the bottom line is first and then everything else comes afterwards.
• 57:10
  SPEAKER_01: And just because something emerges from that space, it doesn't mean it's philanthropic, it doesn't mean it's of no business value, it's just a different context, and that context can cause you to do great things.
• 57:21
  SPEAKER_01: So, yeah, that's my takeaway very much.
• 57:23
  SPEAKER_01: Very inspiring.
• 57:24
  SPEAKER_01: So thank you, Stephanie.
• 57:25
  SPEAKER_00: Yeah, thank you.
• 57:26
  SPEAKER_00: Thanks for listening.
• 57:27
  SPEAKER_00: I think it's been really nice to have a conversation that has been so focused on the patients.
• 57:33
  SPEAKER_00: I'm so used to when I present ultra-rare disease, even the concept of it, people start talking about the regulatory space and how that isn't working and how things should change.
• 57:44
  SPEAKER_00: And maybe it's also because that is changing that we can all step back a little bit from that and and start having the next level of conversation.
• 57:51
  SPEAKER_02: And for me, that is I my mind is still a little bit blown, and I'm trying to digest how to make this like practical in my reality.
• 57:59
  SPEAKER_02: This flipping of the script from starting with the patient and the needs that are already out there, and then developing the treatments uh based on the patient population and not the other way around.
• 58:11
  SPEAKER_02: Little explosions in my brain keep going as I think about why why is why is this not the default?
• 58:16
  SPEAKER_02: This makes so much more sense.
• 58:17
  SPEAKER_02: So thank you for making my my brain uh challenge my previously held assumptions about how our industry is supposed to work.
• 58:25
  SPEAKER_02: And Stephanie, where can our listeners find more information about you, about wincure, and the rest of the cool stuff that you built?
• 58:34
  SPEAKER_00: On wincure.com.
• 58:36
  SPEAKER_00: That is as simple as that.
• 58:38
  SPEAKER_00: Just to protect ourselves, we've also bought win cure medicine, wincure medicines, wincure medicines with a Zed.
• 58:45
  SPEAKER_00: So you can uh just to jazz it up.
• 58:48
  SPEAKER_00: So uh any versions of those will get you there.
• 58:51
  SPEAKER_00: And Rare Key is also on there.
• 58:53
  SPEAKER_00: So if you sit with a patient that you you have to either be the legal guardian or the patient to submit.
• 58:58
  SPEAKER_00: That's just to make sure that the people who submit are actually interested in the being a part of a trial, potentially.
• 59:04
  SPEAKER_02: Please do go to rare key if you have a situation of a rare disease and uh contribute to potentially developing medicine for that.
• 59:12
  SPEAKER_02: Stephanie, thank you so much.
• 59:13
  SPEAKER_02: This has been a wonderful conversation.
• 59:15
  SPEAKER_00: Thanks for having me.
• 59:21
  SPEAKER_02: This was Lab2Lives.
• 59:24
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• 59:31
  SPEAKER_02: What is your take on how we get from the lab to making a difference in patients' lives?
• 59:36
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• 59:41
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