Charles River Laboratories International Inc.

06/18/2024 | Press release | Distributed by Public on 06/18/2024 08:35

S5, E09: Cure EB: Healing the Wounds

Sharmila Nikapota (00:04):
Epidermolysis bullosa, or EB for short, is a diabolical condition. We say that it's hard to say and hell to live with. And especially in its most severe forms, it's like a medieval torture. It's constantly painful and debilitating. And to be blunt, it's like being flayed alive. And yet children and adults are meant to endure it, still with very little effective help. And that has to change. It simply should not exist. Even if you can ignore the sort of humanitarian cost, the economic burden of managing it on the healthcare systems is immense.

The daily toll on patients and their families is acute. And as an EB family, we completely understand all too well the pressures on siblings, within parental relationships and all the relationships around us. The cruelty of the condition cannot be underestimated. The suffering starts at birth, gets worse, and eventually after years of pain and disability, a malignant skin cancer raises its head and robs them of life at sometimes an early age. So that really is the driver. It's a horrendous condition.

Chris Garcia (01:41):
Imagine the exhilarating moment when after 18 hours of labor, you hold your newborn baby in your arms. As you marvel at every detail, you notice an unusual patch on her delicate skin. Initially it's just a curious anomaly. But as the days turn into weeks and medical consultations begin, you come to realize your child has EB, a rare and devastating genetic skin blistering disorder.

As a parent, how far would you go to fight against the clock of your child's prognosis? I'm Chris Garcia, and in this episode of Vital Science, we explore the answer to this question with Sharmila Nikapota, founder of Cure EB and the mother to 22-year-old EB patient Sohana. In this episode, we discuss the complexities of this rare disease, Cure EB's research efforts and the fragility and strength exhibited by pediatric EB patients, earning them the nickname of 'butterfly kids.'

Todd Poley (02:38):
Welcome to Vital Science Sharmila. We're honored to have you. Would you tell us a little bit about yourself and your family?

Sharmila Nikapota (02:45):
Well, I should probably say that my scientific background is in veterinary medicine. I was in practice for a number of years before starting a family. Our daughter, Sohana, was our first child. And when she was born with epidermolysis bullosa or EB, I left practice to look after her. But in addition to Sohana, we have three other daughters who make us a very noisy, happy family. A husband who has had to find his feminine side with all these women in the house and a little dog called Fizzle.

Todd Poley (03:22):
So let's talk about your amazing daughter, Sohana. What are some of the things that make her so special?

Sharmila Nikapota (03:29):
Well, one of the first thing I'd say about Sohana is that she is strong and brave. She will say that it's because she's had to be, but nevertheless, she has handled situations as a child that I would balk at as an adult. She's funny, inquisitive, clever, beautiful, is a talented artist and singer and with a knowledge of music that's quite astounding. Her physical limitations have led her to the arts, and she has a passionate interest in film, which she's studying at university at the moment. But she's very special because she's not limited by her condition.

She kind of pushes herself forward even when pain is extreme or the emotional burden is heavy. She's determined to live her life and not be defined by EB, but it's obviously a constant in her life and an unwelcome companion and one that she cannot escape, of course. One that she would love to be rid of and it brings her down and often makes her sad, but she picks herself up and gets on with it. And it just takes immense courage and fight and I could not be more proud of her.

Todd Poley (04:48):
It's amazing. And that courage had ripple effects, I'm sure for you, which has propelled you to create your foundation, Cure EB. I know it is very near and dear to your heart. Could you tell us the story of how it got started?

Sharmila Nikapota (05:04):
Well, for a time after Sohana was born, we were just trying to get to grips with the condition, trying to manage the condition. We were told when she was born that there would be nothing to help her through her life and that we should just go away and look after her. And we asked, "What does that mean? Do we just go and wrap her in cotton wool?" And the consultant at a rather large university hospital in London said, "Yes, that's about it." And walked off. That kind of response, I think is something that is quite common with rare conditions, and particularly 20 years ago.

Because there was nothing that you could do for genetic conditions. No treatments, no cures. So our kids were, in effect, consigned to the incurable list and stuck on the muck heap of life, if you like. So we did go and do that. We went away and we started looking after her. And in a way, we sort of stuck our heads in the sand until we decided that we really had to try and change that picture. It became obvious that there was very little money going into researching treatments and that more could definitely help. And that's really where our mission began.

Todd Poley (06:24):
So it says that your mission is to accelerate research to end painful skin conditions. So what is the driving force behind your mission?

Sharmila Nikapota (06:37):
So epidermolysis bullosa, EB for short, is a diabolical condition. We say that it's hard to say and hell to live with. And especially in its most severe forms, it's like a medieval torture. It's constantly painful and debilitating. And to be blunt, it's like being flayed alive. And yet children and adults are meant to endure it, still with very little effective help. And that has to change. It simply should not exist. Even if you can ignore the sort of humanitarian cost, the economic burden of managing it on the healthcare systems is immense.

The daily toll on patients and their families is acute. And as an EB family, we completely understand all too well the pressures on siblings, within parental relationships and all the relationships around us. The cruelty of the condition cannot be underestimated. The suffering starts at birth, gets worse, and eventually after years of pain and disability, a malignant skin cancer raises its head and robs them of life at sometimes an early age. So that really is the driver. It's a horrendous condition.

Todd Poley (08:05):
It really is unimaginable.

Sharmila Nikapota (08:07):
It really is.

Todd Poley (08:09):
And we'll get into your daughter's journey. I really wanted to, as you reflect since you've started Cure EB and once you envisioned creating more awareness and education, and to your point, the mission of being a catalyst for accelerating this research. How has your vision surpassed your expectations or the progress surpassed your expectations?

Sharmila Nikapota (08:37):
So to be honest, my dream is not to have EB in this world. My aim is that Cure EB need not exist. So I'm being quite greedy, I guess, in my dreaming. And as such, really cannot say that expectations have been surpassed, exceeded yet. But what is a constant wonder to me is the incredible people who have stepped in to help us along the journey. It's fellow parents of our kids, friends, colleagues, family researchers, donors, people who have absolutely no connection to EB donating year after year because they are horrified that such a condition exists and want to help.

So my thanks really goes to all those people who have helped bringing awareness of EB and have been alongside fighting it from the start. And you believe in cures. I would not have had the strength to fight this fight without an incredible group of parents who've been my volunteer Cure EB team since the very beginning. So I think it is the wonder around people who are willing to help, even though they're not impacted by a rare condition, it's just extraordinary to me. I can't thank them enough.

Todd Poley (10:01):
I think it's something that you see and you don't want these young people to suffer and be in pain and you can't help but join. And it is a contagious rallying cry to come alongside these rare disease families. So I would like to chat a little bit more about your daughter, Sohana. I know she was diagnosed with EB with a subtype for recessive dystrophic epidermolysis bullosa or RDEB. What led to her diagnosis?

Sharmila Nikapota (10:39):
Sohana was born fairly intact with a very small patch of skin missing off the side of her neck, which is quite an unusual presentation for a child with RDEB. Many babies are born with skin missing from limbs, and it becomes a little bit of an easier diagnosis. We were told that there was nothing to worry about and that it might be the cord that was wrapped around her neck. And after 18 hours of labor and a [inaudible 00:11:10] delivery and lots of painkillers at the time, I thought that sounded quite plausible. And we dressed her up in her nappy and baby grow with a little cap.

And it was only till the next morning that we discovered that she was missing the skin off the tops of her feet and backs of her ankles and that there was something quite wrong. But then we discovered the lack of awareness around EB within, again, this very large, very well-known London University Hospital. And it was a bit of a process to work out what was happening. First it was, could it be a bacterial infection, could it be a viral infection? And it was only a bit later on in the day, the dermatologist came along and mentioned the words EB to us. "What's that?"

And eventually the clinical nurse specialist came over from Great Ormond Street Hospital and we had an idea that this is what we were dealing with. And after that, actually we got transferred quite quickly to that hospital. Sohana had a biopsy, after she'd been stabilized and they started dressing her, doing the blisters, doing the wounds, and we had a diagnosis. They did a skin rub test on her and found where the fracture was within the skin layers.

And eventually genetic testing was done so that we knew exactly where her mutations were and discovered that we as parents had given this horrible condition. That that was really the process for Sohana.

Todd Poley (12:56):
So you have your diagnosis. How did that impact your family immediately and how did it influence you to become such a patient advocate that you are today?

Sharmila Nikapota (13:09):
Well, the diagnosis definitely changed everything, all expectations and how we thought life was going to roll out. We have been so lucky as parents in the lives we led, easy upbringings, everything sort of falling happily into place. Then to have to watch your child suffer the most unimaginable pain on a daily basis was a massive shock. I just wanted to take that pain away, but I couldn't. I could only help and try and limit damage as much as possible. So I gave up being a vet. Having a newborn baby is difficult enough, but having a newborn with EB is a scary learning curve.

Everything you could do could cause more damage, feeding, nappy changing, doing dressing, even cuddling. If you are out on a particularly windy day, you could cause an eye abrasion because of the fragility of the corneal surfaces. So you start running a kind of military operation, with endless kinks. And even when going out for a short time, spontaneity is crushed, trips are challenging, and you have to have lots of luggage space for dressings and medications, sheets, pillowcases, towels.

We did go on fairly soon afterwards to have a sister for Sohana, which was fantastic, normalized life for everybody and then twins to add to the fun. But siblings know that they come second, third, and four, their needs are rarely prioritized. And if they fall over, it's very, very difficult to find sympathy for a small graze when you're dealing with a child with very severe wounds. So they've been fantastic. They've coped really well and they're fantastic sisters for Sohana as they have.

Todd Poley (15:24):
So Sohana will be turning 22 this year and has come such a long way. Her childhood journey has been of remarkable resilience and strength. I can't imagine the mental strength she possesses. How has her experience shaped who she is today?

Sharmila Nikapota (15:47):
So Sohana was a little girl with a really sunny little child. She could find humor in lots of things, surrounded by love, went to wonderful schools that really nurtured her interests and made her allowances for her conditioning and allowed adaptations to accommodate them. And not every child has that opportunity in school life. So we were really lucky. When we started a fundraising mission, of course, she had to get involved with that because we had to show people what her life involved. And she knew that she was going to have to appear in films, appear in photos.

She knew that she'd been filmed in very vulnerable positions as well. But in a way, the whole mission eroded her innocence. And she found once something that I'd written on skin cancer when she was very small. And she realized at that time that she was at risk of a short life. She didn't tell me at the time but it played on her mind a lot. And as a young teen, the conditions started to impact her emotionally and started taking a toll. And also having been on the Epson trial where she saw improvement, there was no real follow-on and she felt that she'd been promised change, but that change hadn't really materialized.

She had almost started imagining a life without EB, but that hadn't happened. And understandably, that kind of drew her away from what we were doing a little. She was less keen to get involved and was just trying to manage living. But now, after a lot of work with her psychologist, she still hopes for change, but has accepted EB as part of her life and is working around it as best she can. Going to university was tough to start with. Not having mom doing dressings was a big wrench, having to have a carer, but she now has the freedom knowing that if I go under a bus there's someone else who could look after her as well.

And that gives her a much more freedom, I think. I think where she is now can be best summed up in something she wrote for a fairly recent brochure, which I think is quite beautiful. So if you don't mind, I'm going to read this out to you.

Todd Poley (18:24):
Please. That would be wonderful.

Sharmila Nikapota (18:25):
So this is what she says. "My day is painful, challenging, and often completely unpredictable, apart from the knowledge that I must be constantly vigilant and careful of what I eat, when I take my medicine, how I walk, sit, write, and talk. I also spend around five hours a day dedicated to a skincare routine that I would generally not survive without. Celebrities and beauty gurus have nothing compared to my cupboards of product. One aspect of my day that is also certainty is joy.

Sometimes it appears in the form of hope, the prospect of things improving, but these days it is normally real as I have not only survived the age of 20, but grown into a person who gains confidence from what I endure, use as my experiences to connect with others and flies through the process of breaking down and healing. Brushing the ash off my butterfly wings and continuing to live for as long as I can." I think that's beautiful, but I'm terribly biased and I think it shows where she is. She's living with the hope, but she's just getting on with it.

Todd Poley (19:45):
It's beautifully stated, and I think it's a reflection of her awareness as a beacon for hope. It's a beacon for education into this rare disease. Watching her videos at a young age on your foundation's website drew me in because I think she's had to rapidly mature. She knew no other option, and it's quite an inspiration.

Sharmila Nikapota (20:14):
She's been knowing in a way that children are not normally in going forward, and I have to say, it's often the case with kids with EB. They have to spend a lot of time with adults, and Sohana has known what her role should be from an early age.

Chris Garcia (20:34):
Affecting over 500,000 individuals worldwide, EB is a genetic skin condition that causes extreme fragility, leading to blistering and wounds with the slightest friction. There are four main types of EB, dystrophic, junctional, simplex, and Kindler syndrome. Each varying in severity based on which layer of skin is affected and the specific genes involved. Symptoms can range from surface blistering to deeper tissue damage, thicken skin on hands and feet, nail problems, hair loss and dental defects.

Severe forms of EB can lead to constant pain and difficulty healing wounds. Additionally, EB can cause oral blistering, tongue shortening, esophageal scarring, trouble eating, and constipation. In the most severe cases such as junctional dystrophic EB, corneal abrasions may occur, potentially leading to blindness and significant scarring on the eye surface. Let's hear from Sharmila on how Cure EB hopes to relieve these symptoms through novel therapies.

Todd Poley (21:41):
So as you mentioned, this disease can create other conditions, the toll that the body takes. Can you explain to me what areas of research are being explored for the treatment of EB currently?

Sharmila Nikapota (21:59):
Our ultimate goal is finding a permanent genetic fix. So we fund a lot of gene editing work and hopefully leading on to trials. We're also looking at workarounds, perhaps repeating systemic treatments that could have a huge impact by giving the same result but not needing a change in the DNA. We're particularly excited about one such project in this field. But while all this is ongoing, of course, we are also interested in treatments that can improve quality of life, so exploring more local treatments through gene therapy and gene editing as well as cell therapies.

So that's around something like the Mission EB trial, which is just looking for a dramatic change. And drug therapy is particularly where we're trying to combat the EB associated squamous cell carcinoma, malignant skin cancer for which there is no cure but very high mortality rate. Unfortunately, the survival is next to zero once you are diagnosed with this cancer. So there's a really unmet need there. And there are lots of groups working on induced pluripotent stem cells, recombinant protein therapies, antibiotics, and different mechanisms for pain relief as well.

Chris Garcia (23:29):
Diagnosing EB can be challenging, but it often starts with noticeable skin issues at birth. Doctors typically perform a biopsy and genetic testing to confirm the diagnosis. Severe forms of EB are usually easier to diagnose due to obvious skin loss, while milder cases are sometimes misdiagnosed or mistaken for other conditions. For instance, in some rare cases, a parent with dominant dystrophic EB might have a child with recessive dystrophic EB, leading to confusion and diagnosis.

However, biopsies and genetic testing help clarify these situations. Despite there being no cure for EB currently, ongoing advancements in gene therapy offer hope for improving patient's quality of life significantly. Let's hear more from Sharmila about one such treatment that was recently approved in the UK.

Todd Poley (24:23):
So in 2023, the UK approved the first treatment for EB, marking a milestone and bringing treatments forward for these patients. Could you tell us more about this treatment and how it improves the patient's quality of life?

Sharmila Nikapota (24:38):
So Filsuvez is groundbreaking because it's the first treatment for EB and it's fantastic that it's gone through all the regulatory processes, that it's marked approved and all those things. It's a wound healing cream, so it's not addressing the genetic defects, but it's thought to help wound closure. Now, despite the fact that it was approved in August 2023, still one of our biggest centers in London for adults still doesn't have access to the drug. So that's not fantastic because I'd love to try it on Sohana.

So we're just waiting for it to get to the hospital and be able to test it out. But in terms of getting it through, a huge kudos to Amryt Pharma for getting that drug, that cream approved, and hopefully it's going to be the first in a long line of treatments. And it's definitely made the regulators more aware of epidermolysis bullosa, which is only going to help going forward.

Todd Poley (25:51):
And I believe there should be a sense of urgency with giving access to these patients here, because I imagine the daily management for patients and caregivers is strenuous. Could you explain a little bit more about what that daily management looks like?

Sharmila Nikapota (26:10):
It's a grueling regime. If I look at each day, or we'd start the day with Sohana, first of all going into her bedroom, putting [inaudible 00:26:21] on her eyes so that the light doesn't cause a sudden shock and cause a corneal abrasion. That's literally the first thing we'll do. And then she has to have painkillers, and then we start checking under her dressing as we do that twice a day. So the dressing changes on a daily basis, take between three to five hours, depending on whether it's going to involve fully taking off all the dressings and putting them back on.

And this is terrible for the patient because it's painful. You have to prick the blisters as they appear, dress the wounds, reapply the dressings, bits of dry skin, and it's absolutely horrendous for them to have to go through this process. And for the caregiver, particularly if it's a parent, it's horrible because you're having to hurt to help. And that often leads to a bit of a battle. If a painful blister needs to be pricked, then you have to hurt your child, and that's not what parents want to do.

And it can lead to feelings of desperation, to be honest, when you're going through this, because you just want that to end. So there's the daily pain management. There's having to blend food for eating because getting the calories in with just normal solid food is quite difficult. The esophagus is vulnerable so that you can cause scars and strictures in the esophagus. The mouth is painful, tongue as I said, is shortened, and there are often blisters in the mouth. So eating can take a long time.

Some children have gastrostomy tubes to aid feeding, and this helps nutrition, but it often isn't a pleasure. It's a chore that has to be accomplished by the child. It's amazing to me that Sohana enjoys tasting different foods, but more often than not, she's eating something blended, like a thick soup just to be able to get the calories in. There are lots of hospital visits, visits to the multidisciplinary team, physiotherapists, nutrition, dieticians, ophthalmologists. The number of professionals that are seen at these appointments is huge.

Todd Poley (29:02):
And you've touched on the power of many. Often with rare diseases it is a long effort to build a sense of community, especially in the research drug discovery and development community that will take on this work. And we know that it is the power of uniting drug development with high novel research partnered with the commercialization, the accessibility for patients, and the high costs that can be associated with this.

I wanted to ask a little bit more about, we referenced the topical cream that is out there today, but we know that the restrictions are challenging. How can we make therapies more accessible to the patients who need them?

Sharmila Nikapota (29:51):
That's a really sort of critical area for patients with rare diseases because they may at some point have an effective treatment developed that is not commercially viable. To have the hope of being treated, but no one willing to pay for the treatment. But with the EB, the challenge is that there are four different types and many different mutations on single genes that can cause a spectrum of the condition. And different genes involved linked to various types so that the one-size-fits-all approach is more difficult to find in a way that makes investors in biotech happy.

Because we also have a relatively small patient numbers and the high cost of development, particularly if you are looking at things like viral vectors. There are just so many different hoops to jump through. And you touched on B-VEC, the topical cream now available in the US, which is a gene therapy cream. It's a treatment for dystrophic patients, both dominant dystrophic and recessive dystrophic EB patients. It's a repeating treatment. It doesn't address the internal problems associated with EB and only treats wounds, but it is meant to give more prolonged healing.

We haven't trialed it in the UK yet, and it is being used in the US, but it is really expensive. It's a very expensive drug. And I think it is in part a pricing issue that's taking its time, getting it through in the U.K. So we have the two treatments approved and on the market as it were, but we don't have access. And in no sense is this addressing the hundreds of thousands worldwide with the condition. So it is kind of what is the solution as we go forward into developing treatments for rare conditions.

And in addition, some big pharma have pulled their rare disease programs, which is really sad to see, but that kind of leads a very vulnerable population suffering, in Europe alone, 30 million, and the states all suffering from rare condition. And the way we try and look at this is to, in a way, de-risk the process by taking some of the costs associated with the early stages of development. So focusing on the kind of value of death, area between the bench and the bedside.

So in early phase one and two eight clinical trials, getting proof of concept, that means going through animal models, testing early phase clinical trials, building value in a treatment modality, and hopefully exerting some kind of control over how it could be used. If I take recessive dystrophy EB as an example, there's so many different mutations that lead to the condition, and some of these occur at common points, but some are completely individual.

And for those individuals, their solution might be in personalized medicine. The common could potentially be marketable, and we would hope to create an upside from those marketable common areas if you like, to then pay for the more unusual. And we hope that when a commercial partner is needed, and that's almost inevitable when you're talking about scala, then we'd like to find an ethical commercial partner to help bring the drugs to the market, preferably without the massive price tags that would make healthcare providers more keen to pay for the treatment.

But perhaps it is more incumbent upon governments to put aside the traditional approach of needing commercial trials with X number of patients on them to give value to treatment and understand that this is a critical situation for most patients with rare condition. It is critical in the same way to me that Covid was critical. There's no time to waste. There is a dire need. The early access by compassionate use mechanisms should become more commonplace for clinicians to get patients treated in this way if you have a treatment that's seen as effective.

We saw how regulations were pushed aside through Covid and for patients with EB, I think it's a crisis of the same scale. The arena is changing around personalized medicine, and in the UK we have the rare disease launchpad that is trying to bring n=1 treatments to neurodegenerative conditions, and it's really great to see it. I hope this in some way will apply then towards other conditions as well. I'm looking forward to delving more into that space coming in the future.

Chris Garcia (35:40):
Fundraising plays a critical role in advancing research and treatments for EB. Cure EB relies on donations from private individuals, grants from foundations, and innovative digital campaigns. The funds raised are primarily allocated to research initiatives aimed at finding a cure for EB. The organization works to maximize the impact of every dollar raised by ensuring an efficient use of resources. Collaboration between patient advocacy groups, researchers, and regulatory agencies is essential for driving change and facilitating access to treatments, especially for rare diseases like EB.

This collaborative approach aims to reshape traditional models and prioritize patient needs even if treatments are not commercially viable. In the UK, there is a unique initiative known as the Rare Therapies Launchpad, which serves as a model for advancing research and treatment development, particularly for conditions with limited patient populations. This initiative emphasizes the importance of individualized approaches to drug development, recognizing that even treatments targeting small patient groups can have a significant impact on those affected.

However, as research progresses, there will be costly hurdles ahead, such as a need for extensive toxicology testing, further underscoring the continued importance of fundraising efforts in Cure EB's work. Let's learn more about where Cure EB's efforts are focused for the future.

Todd Poley (37:06):
So let's look towards the future. In your opinion, what does the future hold for rare disease drug discovery and development?

Sharmila Nikapota (37:15):
Well, I think it's a really exciting time. Gene therapy is becoming more commonplace with first approved gene editing drugs on the market already. You would've even thought that. The field is moving incredibly fast, and I believe this is the time for genetic disease, so long incurable and forgotten. And now the potential is there to make that huge difference and find the path towards treating as many patients as possible with as many rare diseases as possible.

If we can find a way economically to be able to do that. And I think in the end that is to the benefit of all and obviously, not least to those who are really, really suffering at this point.

Todd Poley (38:06):
And what does the year ahead look like for Sohana?

Sharmila Nikapota (38:12):
Well, I hope Sohana will get into her third year at uni and stay focused and happy. That really is the most important thing for me, to see her happy and as healthy as possible, pushing aside a condition where she can and just getting on with it and hopefully sooner rather than later, we'll have something that will make her feel a lot better.

Todd Poley (38:39):
Absolutely. And how about Cure EB and the many initiatives you are involved in as a active patient advocate?

Sharmila Nikapota (38:48):
Well, we just need to work as hard as possible to get some of these exciting things to patients as soon as possible. So pushing as many avenues, building the collaborations with the scientists, other genetic conditions, other families, and just... I think with the EB, there are so many different assets. The condition, there are lots of different avenues to go down, and it's finding some of those common avenues and having people working on different areas I think really helps that we can push the resources in a variety of different ways.

To get symptomatic relief, quality of life change, and for us, eventually genetic fixes and eventually cures. That's really what we're doing. We want to maximize awareness, maximize funding for research, and just do what we say, accelerate it as much as possible, get those treatments out there.

Todd Poley (39:53):
Quite a legacy that will be. Absolutely. How can our listeners help you get there?

Sharmila Nikapota (40:00):
Well, by sharing our stories, by giving us advice, suggesting things that we haven't thought about, by donating where you can. And if you're a billionaire, do something really amazing. "I helped to Cure EB." That's what we want everyone to be able to say at the end of the day.

Todd Poley (40:27):
I hope we get there soon. Sharmila, thank you so much for joining us on Vital Science and sharing Sohana's journey and educating us on EB, and we just really are grateful for your time.

Sharmila Nikapota (40:43):
Well, thank you very much for having me on here, and nice to meet you all.

Chris Garcia (40:47):
Sharmila Nikapota is the founder and trustee of Cure EB. We will be back next month for another episode of Vital Science. Until then, thanks for listening. Did you know that Vital Science recently launched a new limited series called Bold New Approaches? The series focuses on the voice of current perception of NAMS, the convergence of science and tech, alternative methods in regulatory and the road ahead for therapeutic developers.