TRANSCRIPT
Deborah Borfitz:
Hello and welcome to the Scope of Things podcast, a no-nonsense look at the promise and problems of clinical research, based on a sweep of the latest news and emerging trends in the field and what I think is worthy of your 30 or so minutes of time. I'm Deborah Borfitz, Senior Science Writer for Clinical Research News, which means I spend a lot of time with my ear to the ground on your behalf and a lot of hours every week speaking to top experts from around the world. Please consider making this your trusted go-to channel for staying current on things that matter, whether they give us hope or cause for pause. In another five minutes or so, I'll be speaking with Annette Bakker, CEO of the Children's Tumor Foundation, about what nonprofits uniquely bring to clinical research and new financial models for sustaining their contribution. But first the latest news, including a new approach to funding clinical trials for ALS, an algorithm using spatial biology biomarkers to match patients to trials, development of a biomap of lung cancer tumor changes, improving diabetes treatment outcomes for patients in China, the possibility of slowing Parkinson's-related dementia with cough medicine, and how the UK is uniquely overcoming some of the timeline-related Earl hurdles in Europe.
Deborah Borfitz:
A new financing model has been proposed for developing drugs for amyotrophic lateral sclerosis, or ALS, to bridge the notorious valley of death whereby promising scientific discoveries often fail to translate into viable therapies. The so-called Fund of Adaptive Royalties approach merges the efficiencies of adaptive platform trials, which allow multiple drug candidates to be tested simultaneously under a single master protocol, with a fund that rewards investors with future royalties from successful drugs that emerge from the trials. A simulated fund of this type generated an estimated return of 28%, with a 22% probability of total loss, making it potentially attractive to hedge funds, sovereign wealth funds, family offices and philanthropists. Returns more palatable to mainstream investors might be generated by funding multiple platform trials simultaneously and employing financial tools that bundle future income from assets like loans or royalties into investment products. Researchers at Virginia Commonwealth University have been working with principal investigators across campus to include spatial biology biomarkers in their cancer clinical trials, to predict patient responses prior to enrollment and, when individuals can't be part of a trial, point them toward already approved drugs that could help. The guidance is provided by TACIT, short for Threshold-Based Assignment of Cell Types from Multiplexed Imaging Data, an algorithm that assigns cell identities based on cell marker expression profiles and, thanks to artificial intelligence, does the job in minutes rather than weeks. Tacit distinguishes cells using data from over 5 million cells across major body systems like the brain, gut and oral glands. In a new study, it was found to outperform existing unsupervised methods in accuracy and scalability, while revealing new cellular associations, and the results strongly agreed with genetic and protein datasets. I'm writing a piece on this for Diagnostics World News, so be on the lookout for that to learn more.
Deborah Borfitz:
City of Hope was recently awarded close to $24 million from the federal government to create a biomap of tumor changes that cause immunotherapy resistance in advanced or metastatic non-small cell lung cancer. As part of a national precision cancer therapy program, it will be conducting a six-year 535-patient clinical trial designed to adjust treatment as resistance arises, with the goal of increasing progression-free survival by 50% in at least one patient group. Investigators will monitor tumor trajectory and patients' response to treatment using techniques like liquid biopsies, single-cell sequencing and radioimaging. They are also funding the development, testing and matching of new biomarkers with therapeutic options currently available or in a clinical trial. Trial enrollment begins within 12 months. A large-scale pragmatic clinical trial has launched in hospitals across China, designed to improve treatment outcomes for patients diagnosed with diabetes by using a Chinese-specific version of the genetic risk score to distinguish between people with a type 1 and type 2 disease variety, since patients in the region often don't fit the classic Asian weight profile with which the diseases are diagnosed, and about 25% of individuals with newly diagnosed type 1 diabetes lack detectable islet autoantibodies measured by early detection tests. Misdiagnosis of the type 1 adult onset variety, whereby the body's own immune system attacks insulin-producing beta cells in the pancreas, means delays in getting daily insulin injections to avoid complications. Type 2 diabetes, which could be triggered by high body mass index, has several treatments and nearly half of patients with a short disease duration may succeed in achieving disease remission.
Deborah Borfitz:
A landmark study in Canada has found that a cough medicine used safely for decades in Europe could potentially slow Parkinson's-related dementia. In the year-long clinical trial involving 55 participants with Parkinson's disease dementia, ambroxol was found to be safe, well-tolerated and reach therapeutic levels in the brain. Moreover, in the treatment group, psychiatric symptoms remained stable, as did a blood marker of brain cell damage, and participants with high-risk GBA1 gene variants showed improved cognitive performance. Researchers plan to start a follow-up clinical trial focused specifically on cognition later this year. And finally, investigators have identified major ethical, administrative, regulatory and logistical barriers, or so-called URL hurdles, for multinational clinical trials in 19 European countries, based on an analysis of data from an international platform trial testing multiple drugs for the treatment of pneumonia between 2016 and 2023. The analysis was focused on three key metrics time to complete site contracts, time to regulatory and ethical approval and time to first patient enrollment and pronounced differences were found in studies conducted in the UK versus non-UK countries. Notably, the UK achieved dramatic gains on all three timeline-related measures during the pandemic, far outpacing that of the other geographies which researchers credit to the country's established research networks and emergency trial frameworks. As a reminder, links to all the articles, studies and press releases covered in this month's news segment are only a click away in the show notes.
Deborah Borfitz:
It is now time to bring in Annette Bakker, head of the Children's Tumor Foundation, to talk about the evolving role of nonprofits in the ever-time and cost-challenged R&D ecosystem. Welcome to the show, annette. Thank you so much, deb. This is so interesting. Thank you, you are so welcome. When we last spoke a few months ago, one of the things that stuck with me was your motivation for pivoting from industry to the nonprofit sector, where there is a shared, as you said, urgency with patients to get to answers rather than to get published or keep things secret. I was hoping you could start us off by sharing that tale with our listeners, because I think it gets to the heart of the work the Children's Tumor Foundation is doing, in this case for patients with neurofibromatosis or NF. Can you oblige?
Annette Bakker:
Sure, absolutely Very happy to do so. So, just historically, I was about for about a good 10 years in academia, followed by a good 15 years in industry, and what I noted is that the industry sector has excellent drugs and the academia has excellent models, and the models are anything from cell models to animal models to anything. You need to bring the good treatments to the patients, and so if these two come together the drugs and the models then you can start thinking about better treatments for patients. Unfortunately, that is not the case. Very often the models are let's now say for the lack of a better word stuck in academia, because in the academic enterprise, people are driven by curiosity and it's a lot about publications and it's a lot about making sure that you keep the funding for your lab. That is all dependent on what you discover. On the other hand, the industry people they are very laser focused on drug discovery. However they are there, let's say, modus operandi is that they patent their drugs and need to keep their data and their information secret as long as possible. And on top of that, in the industry you as an individual don't per se exist, it's more a team sport.
Annette Bakker:
So when I was working in the early 2000s in Italy in a biotech in Italy in the glioblastoma space, I discovered that in fact, the models that were used to do drug selection and that were accessible to us as pharma people were not good models, whereas the good models, the good animal and cell models, were actually in academia and there was this constant blaming back and forth between academia and industry where, in fact, at the end of the day, the patient was the one who was really suffering, because of course, if we screen on the wrong, however accessible models, we are obviously going to select the wrong drugs and we will not get the right drugs to the patient.
Annette Bakker:
So, being a little bit frustrated about that ecosystem and about the fact that these two kind of stayed in their comfort zone, the opportunity came up for me to join the Children's Tumor Foundation as the then chief scientific officer and what I very early learned is that, as a non-for-profit coming from pharma, you know the disease pretty well, you know the ecosystem pretty well and you can really add a different value than patient support. Nothing wrong with patient support, but I think you can really become a partner in the R&D ecosystem as, let's say, a nexus between, on the one hand, the patients and, on the other hand, all the stakeholders, right from academia to industry to regulators, so you really don't have any conflict and can push everybody a little bit out of their comfort zone to make sure that we're selecting the right drugs to go to the clinic.
Deborah Borfitz:
Got it and I'd love to revisit specifically that what you would call the shelved asset problem, whereby a lot of great drugs are effectively being trashed because they don't meet a company's commercial or strategic business goals, or because they buy a basket of assets from biotech and focus on only one of them and sort of ditch the rest. Please share your views on how a nonprofit like the Children's Tumor Foundation can step into that gap to become a true R&D partner with a pharma company.
Annette Bakker:
Yeah, thanks for that question. I think the shelved assets is a very interesting problem is that pharmaceutical companies a lot of pharmaceutical companies are working on very similar mechanisms and very similar molecules and so when there is the observation that maybe another pharmaceutical company is ahead or is closer to approval, the big pharmaceutical companies and the small ones actually shelve that asset for anything from commercial to strategic reasons. So for me, a shelved asset is not an asset that is shelved because it's toxic, right. Those are the assets that should never come anywhere close to the clinic. For me, the definition of a shelved asset is an asset that still has IP, that still can be great for any other disease than for which it was being developed, that still has a commercial value, so that there is a real justification to get these assets back into, let's say, active development.
Annette Bakker:
The challenge is that for a pharmaceutical company, especially focusing on the rare diseases, that is a really hard place for pharmaceutical companies. Why? Because, first of all, there is thousands of rare diseases. The second thing is that the companies for them, this ecosystem of that specific rare disease, is really unknown. There is very few researchers, there are very few models and once an asset is shelved, the project team within the company is, let's say, reassigned to other projects, leaves the company. I mean there is a whole reshuffle of these experts that were working on these shelved assets that in fact there is not really anyone left to care about these assets. And that is where I could see an organization like the Children's Tumor Foundation come in, or another nonprofit, obviously, to really act as an R&D partner for these companies in a couple of ways.
Annette Bakker:
One, we, for example, specifically at CTF, we do what we call target and drug scouting, which means that we looked at what has been published, Then we look at for what has been published as new molecular mechanisms. Are there any drugs that exist that could potentially benefit our patients? We know the disease really well, but we also really know well the community, and so we have built what I would call an NF therapeutic accelerator that is composed of two elements. One, there is a preclinical hub and we have a dedicated staff member who runs the preclinical hub that if a drug gets identified, she exactly knows in which models they should be tested, which models we can have access to, because a lot of the agreements have already been, let's say, mapped out with the academic institutions. So that is a way to really accelerate the preclinical, let's say, de-risking of that molecule and then couple that to also what you just mentioned the platform trials in ALS. We have also a multiple platform trials now for NF.
Annette Bakker:
So the idea is can we make sure that we kill this drug fast? Right that if a drug doesn't make sense, it's not a good drug for our patients. Let's make sure that we get that drug as quickly as possible out of the door, because there is one thing that we have in common with the pharmaceutical companies is that we want to be fast, just like what companies want, and we want treatments for our patients, and so those two wishes align really well. And I know that the academic institutions are also interesting in making sure that their science actually translates into better treatments. So it's a way of bringing the world together and stop having people locked up in their little boxes, but really bring that human factor as well into the mix, with the patients at the table and no longer on the table.
Deborah Borfitz:
And on a very related note, I'd like to turn to the idea of creating a centralized drug vault where companies might be incentivized to deposit their shelved assets rather than letting all the accumulated data quietly gather dust. I know this wasn't your idea, but could you perhaps explain the premise and why you think it might work, wasn't?
Annette Bakker:
your idea, but could you perhaps explain the premise and why you think it might work? Yeah, so, first of all, my very first experiment was there was actually a drug that was at Pfizer in the, let's say, 2015, 2016,. That was a drug that would really be able to help our NF patients, a drug that would really be able to help our NF patients. That drug was shelved by Pfizer and we wanted to prove that it was possible to get a drug that was actually shelved, to get that back into commercial.
Annette Bakker:
So we work literally directly with, at that time, the head of Pfizer Cures, lara Sullivan, and Frida Lewis-Hall, who was the chief medical officer of Pfizer at that time, to make sure that we assemble a team of people that would make sure that they get the data they were looking at, getting the necessary investors and making sure that that drug was not forgotten. And the reason why we identified that drug is that we already had generated, within the academic institutions, good clinical data for that molecule, so that molecule was really well, let's say, de-risked for NF and so, as of, let's say, as a case study, we were able to help these people to make sure that that drug got out of Pfizer into a new company, springworks, and then the Springworks team did an excellent job getting that drug all the way to approval on February 11, 2025. Now this company, springworks, was just acquired by Merck, the German Merck, for $3.5 billion. Merck the.
Annette Bakker:
German Merck for $3.5 billion. So the reason why I'm telling you this story is that this is the story that, yes, you can get the drug out of a pharmaceutical company, yes, you can create a new company around it and yes, you can get it approved and, yes, you can make money. The challenge, and what makes this so difficult, is that this the way we did this, let's say case study is not scalable. To give you an idea, frida and Laura managed to get 200 volunteers at Pfizer, who worked day and night on their weekends to make sure that the necessary data on these shelved assets were collected, organized and usable to spin out a new company. So you're dependent on 200 volunteers, which, of course, is a very unique thing, but is not a very scalable thing. So that is where we then came up with the idea and where, in fact, now we're working together with Professor Andrew Lowe, dr Frida-Louise Hall, dr Tanisha Carino and myself to figure out can we create a vault so that the shelved assets can be together in one organized way that we don't have to redo the 200 volunteer experience every time we have a shelved asset? Do the 200 volunteer experience every time we have a shelved asset?
Annette Bakker:
The other challenge that we're trying to solve here is that it is very difficult to know which assets were shelved in a pharmaceutical company or not. So it is also. I think the number of shelved assets that people are talking about are highly underestimated. I think they're way more so the ideas. We're working now on this project to create the vault. Dr Lowe is looking at building a business model to also get a return on investment. Tanisha is focusing on the policy side of the world. Can we do something? Frida is the one who did it, so she is really our brain trust to make sure that we are getting these assets to something that is valuable and then I see where CTF and other foundations can really participate is to act now as the riskers and build these R&D accelerators to make sure that companies don't, between brackets, waste time on agreeing and making sure that we get the necessary paperwork in place to even start doing the drug testing right.
Deborah Borfitz:
Yeah yeah, yeah, definitely keep me posted on progress. That is super exciting and very innovative.
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Deborah Borfitz:
Meanwhile, the Children's Tumor Foundation has, in fact, some active R&D accelerators. You just referenced one a moment ago. Can you talk a little bit more about that? And I think there's a great deal of emphasis on patient-centric platform trials in particular. Yeah, yeah, the value of all that.
Annette Bakker:
Well, the value of the preclinical hub is really to make sure that we get a drug very quickly from we don't know what it's doing to it's working or it's not working, because, especially for the biotics, they are on very short runways, specifically in the current investment environment that we are in, the faster they can know. Whether a drug has I always say has legs, yes or no, right, could make it through the clinic or not is something that you need to know faster, sooner rather than later. The problem with a lot of these is the agreements, in getting the necessary legal agreements and lawyers in the room to agree on conditions and on everything that actually delays the onset of the trial scares, especially the small biotech. So they will just not do it because it takes too long. So we have that is, in fact, the reason why we've built this preclinical hub. That is, in fact, a network of both public and private partners. Both academic labs and CROs are members of that preclinical hub. The hub is constantly expanding, but we have that one call it expert in preclinical development who really acts as a tour guide right to the pharmaceutical companies. There is this drug and they and that person will be able to say go do this, don't do this, etc. Etc. So that is, in fact, the reason of the preclinical hub. On the clinical side, we have two platform trials up and running one for NF2-related schwannomatosis and one for pain in schwannomatosis. And then there is one that we're now building in Europe, which we hope to get off the ground within this year, which was funded by the European community, called EU Pearl, and where we really would like to build a same platform trial platform basket trial actually where you can look at multiple indications with multiple different drugs in a master protocol that is up there for many years.
Annette Bakker:
Okay, the patient-centric. I just want to give you one thing on the patient-centricity. Yes, I think it is so interesting that we get asked from the morning to the evening whether we prefer peanut butter or strawberry jam, but when it comes to healthcare, nobody asks. You get told what is going to happen to you, and no, and the patients don't ask the questions and the clinicians are not always used to communicate with the patients about their trials, and so what we have done is really figure out a way to make clinical trials more patient-centric and not just have a patient in the room as a token, but really have a patient or a parent in the room who actually participates in the design. And I'm going to give you a very simple example.
Annette Bakker:
If, for example, your child has a glioma, a three-year-old child has a glioma and the clinical trial requires to do a MRI. Just giving you this example now, right, mri every three months. That means that your child of three-year-olds will have to be in anesthesia every three months. Parents may say, no, I'm not doing that, that's too much for my three-year-old. What if you get a conversation and you agree with the clinicians that you would do an every six-month MRI and then the parents are like, okay, twice a year, every six months, I can live with that. Now you have a patient-centric trial and now you get the trial that opens and your patient recruitment will not be a problem. And I think this is so important to get these kinds of conversations going, because 30% of the clinical trials in rare disease fail because the companies or the sponsors cannot recruit their patients in time.
Deborah Borfitz:
Yeah, very, very good points. And besides these patient-centric platform trials, I know the NF Clinical Trials Consortium is another way NF trials are getting efficiently conducted and, as we speak, I also know that, being a congressionally directed medical research program, it is potentially subject to funding cuts. But, that aside, tell us about why this consortium matters and deserves financial support.
Annette Bakker:
I think the most important thing to understand in rare disease is that not one single center sees enough patients to run a clinical trial by itself. None of them. If you would do a breast cancer trial, you could do that in one center, but an NF trial can never be done in one center for the simple reason that there is not enough patients in any of the centers. So you need multiple centers. And the way to make sure that these clinical trials are run in an efficient way and in an effective way you need to set up a consortium of clinical trial centers that actually do collaborate, that they all measure the endpoints in the exact same way that walking three minutes or anything that needs to be done at the clinical trial measuring hearing, measuring movement, measuring anything that that is done and agreed upon by the clinicians to be done in the same way. So that led, in fact, to the birth of this NF Clinical Trials Consortium over 10 years ago now, where today there's about 20 clinical trial centers that are working together if it's not more than 20, that are actually discussing clinical trials, agreeing on the clinical trial design, sharing the data in one place, having the operations in one place. So this is just a super efficient way to run clinical trials that otherwise you would have to go and you would have to assemble all these different trial centers to be able to run to agree every time you run a new trial. So it is a fantastic infrastructure that has been built with money from the congressionally directed medical research programs, from the specific NFCDMRP program and, yes, it got cut. We are heavily advocating to make sure that we can, that this program would get back up, because, if this government is about efficiency, this is efficient. This is very efficient.
Annette Bakker:
I can tell you that a typical clinical trial runs anywhere from $5 to $10 to $15 million per trial. This clinical trial consortium ran, I think, 29 clinical trials with about $15 million. So now here you go. You're about speaking about maximum $1 million per trial to do these trials. And why is it so cheap? Because, honestly, the institutions have put in a lot of volunteer time. These clinicians are amazing. They put in a lot of volunteer time institutions co-fund. So it's really an ecosystem that is super efficient in making sure that we run clinical trials together and it's a prototype for rare disease, if you ask me. So there is the platform trials on the one hand, the clinical trials consortium. On the other hand, I think with those two we will be able to run the clinical trials and I will keep advocating to make sure that this program doesn't get cut.
Annette Bakker:
You have a strong case there, annette, I think so I think so, yeah, it's just about efficiency, right, and it's about building prototype and prototypes in case studies for rare disease, and the reason why this clinical trials consortium is so important is because there are certain studies that are not of interest to the pharmaceutical companies A drug that was already approved for many years, a drug that is off patent, certain things that don't have, per se, a commercial value, but have a huge patient value, and so this is where I think the government should be investing their money in things that matter to patients but don't always lead to return on investments.
Deborah Borfitz:
Yeah, yeah, yeah Makes total sense to me. I love your thinking and, I have to say, I also love another idea that you previously shared with me about how to better inject capital into early stage biotechs a biotech focused on rare disease by building I think you called it a financial continuum to reward their progress and that of their nonprofit partners, step by step. I think I'd like to end today's chat with that hopeful vision. Does that sound good to you? Sounds perfect.
Annette Bakker:
So I say this also with some of my friends who are in the nonprofit friends CEOs, michael Hunt, mark Reutemeyer, from the Alzheimer's Drug Discovery Foundation we are in fact together thinking about ways of being part of also a financial continuum, and let me explain what that means. So we, for example, as a foundation, we are not wealthy wealthy, but we can put enough money in there to get an idea from a non-investable brilliant idea into an investable brilliant idea, and we have done that for many, many years. When it comes to the academic researchers, small grants to be able to create the preliminary data set that they need in order to then get access to the bigger funds from the NIH, cdmrp, any of the bigger funding. And I was thinking in the biotech space that we're, in fact, exactly at the same point where some biotechs have brilliant ideas but they don't have the conviction, they don't have the, let's say, data package that they need to convince relatively risk-averse investors these days to put in money and to help make that idea happen.
Annette Bakker:
So what if the R&D foundations really come in early and a lot of us are doing this right, giving money to this non-investable brilliant ideas from the biotechs and get them to a point where we then create a financial continuum with the investment community when we can say okay, mr and Mrs Investor, you have more money than me, but I can de-risk it.
Annette Bakker:
And can we create so that we can pass these great de-risk ideas on to you who have more money, and then you pass it on to one who has even more money? So really creating that financial continuum, just like we create a research continuum right, it's like building pipelines that's, in fact, my big dream. But we would need the investment community to come together and to partner with us and say we are with you, we are willing to inject some capital to help you de-risk, because my real dream is to become autosufficient, that in fact we make enough money that comes back to the foundation, that in fact this becomes a kind of flywheel of research pipeline and financial pipeline and that we can bring these treatments to the patients that so deserve the treatments that we're developing.
Deborah Borfitz:
Well, I absolutely love your vision of this new kind of ecosystem, annette, and it has been an absolute delight having you as a guest on today's show. Thanks for taking the time to share your passion for finding answers for patients with NF, as well as pointing to a way forward where nonprofits function more proactively and sustainably in the clinical trials enterprise. I hope we can speak again with news of a cure or at least better ways to manage the many symptoms and complications of this perplexing disease, and really just everything that you are doing for the larger world of clinical research and patients in general.
Annette Bakker:
Thank you, thank you, thank you so much. I just wanted to close with an invitation for my companies and the investors to really look for those foundations that are more R&D and patient-driven but science foundations and let's work together. We can do it. We are playing a very unique role in the R&D ecosystem from, on the one hand, being with the patients and caring for the patients and bringing in that human factor, that it's about people, it's not about a scientific problem, and then, on the other hand, kind of really connecting that to the investment in the pharma sector. Let's do it.
Deborah Borfitz:
Let's do it, okay. Thank you again, Annette, and, as always, a big thank you to everyone out there for listening in. If you're not subscribed to this podcast yet, please consider going to Apple Podcasts and doing so right now, so you don't miss your monthly dose of news and perspectives. You'll be hard-pressed to find anywhere else and if you're up for it, I'd also be so very grateful if you'd leave a rating and review while you're there. One more thing before we go, if you'd like today's conversation. It is only a glimpse of what you can expect from SCOPE Europe. Presenters and panelists, please plan to join us October 14th and 15th in Barcelona when clinical operations executives will be exploring the latest trends in clinical trial innovation, planning and operations. Save an additional 10% off any current rate by using the code SOT10. For more information, visit scopesummiteuropecom. Bye for now.