Experts gathered virtually at the Advanced Therapies Integrates 2021 conference recently to discuss the future of the sector. Health Tech World sat in on the debate, which is summarised here.
Debate chair Jason C Foster, chief executive officer and executive director of Ori Biotech, began the event by outlining the subject matter; ensuring that advance therapies reach all of the patients who need them, and how to democratise access to ensure they live out their therapeutic promise.
Jason Foster: “Our mission as a company is to enable widespread patient access to advanced therapies and I’m really interested, in the first instance, to discover our panellists’ perspective on what are the key challenges in the short term?”
David Blakey, senior vice president of strategic alliances at MiNA Therapeutics, said: “From my perspective, there are always challenges in manufacture and cost of goods often can be seen as a great challenge for early technology. And yet I can tell you that, for polygon nucleotide therapeutics, the cost of goods has plummeted, because the dose and time interval of dosing has gone down dramatically. So one of my messages is don’t worry about cost of goods early on, but do think about manufacturing.”
Jason Foster: “Another question I have is how applicable is our past experience to what we’re going through in the future?”
Brian Harrison, managing director, HiTech Health: “I agree with David, I think time will drive down the cost of these personalised medicines, but there’s a lot of work to do, and the complexity of the supply chain is another issue.
“Personalised medicine, taking samples from patients, putting them back in patients, is very complex; we have a number of clients whereby the patient is scheduled in for the treatment first before manufacturing starts. So you’ve got to work backwards.
“Climate change is another big factor, because many of these treatments are not from one single manufacturer, and in some cases, people carry the treatments from one location to another.
“And regulatory issues with new treatments are a big challenge at the moment. For example, one product we’re working on got clinically approved in one country in Europe quite easily but in another really struggled to get treatment past the authorities. So those are a few of the challenges we’re dealing with.”
James Kusena, head of bioprocessing at MicrofluidX: “I think one of the key challenges is sharing the knowledge that is out there and helping the industry to mature at a sustainable pace.
“There are many avenues that people are working on, but in order for these therapies to have a full impact, we need to pick up the people and the supply chains, and also the adoption and reimbursement structures and, of course, the science, so it all needs to marry together.
“For instance, with point of care manufacturing, are the skills there to ensure that the load is as intended for reimbursement? And also, in terms of the science, do we have the right tools to do the work and also the analytics to get better understanding of the processes?
“We try to start with the end in mind, and think about how to scale up for manufacturing, and how that product is going to be sustainable. Do we understand the process enough to ensure that the therapies are going to be robust? Are the costs good enough to ensure that we can enable that wider access to the patients that actually need them?”
Keith Muir, founder and director of Cytomos: “There’s a point I’d like to make about economies of scale, about trying to get the access to these therapies to as wide an audience as possible.
“We’ve got cures to cancer in our hands today, but they might fail because the strategy just isn’t there.”
Krzysztof Potempa, founder and CEO of BRAINCURES: “Where we have the challenge in both biologics and small molecule discovery is the biology of the target that we are developing the drug to. And this is where analytics comes in: if it’s a novel biology, it can essentially de-risk and speed up the process, reduce the amount of experiments you need to do, which will get the cost of the therapies lower if we fail less.
“I would also say that analytics based on artificial intelligence plus novel biology will be key to more personalised medicines in the future, for example in gene therapy.”
Jason Foster: “I’m interested in talking about the journey between data to information, and then information into insights. And those are three different things. So how do we leverage those digital tools that have been adopted by many other industries, to bring into advanced therapies?
James Kusunu: “One of the things we’re very keen on is the integration of getting the data and actually knowing what to do with it and what it tells us.
“So, we’re looking at bringing more things in line and outline so that it’s easier for people to occlude that data, and then having the expertise in terms of the data scientists to actually decipher that and pick out the golden nuggets.
Keith Muir: “Building on James’s point there, and your point, Jason – what is insight, what is information and what is data? So again, let’s start with the end in mind and think, okay, ‘what is the clinical outcome that this is trying to achieve’ and work back from there.
“The second point is actually measuring the product; with oxygen, pH, glutamine and things, they’re indicators of a cell’s health. They’re not measuring cells directly. So they are the paradigms where we can actually start measuring the product.
“The third point is that they become and remain economically viable; as David said earlier, the cost of goods sold will go down in time. But that’s only if we start with that manufacturability, and potentially those clinical outcomes being exactly what we’re planning from the very get-go of developing and therapy.”
Jason Foster: “What are you seeing around the therapy development side, related to these challenges?”
Brian Harrison: “I touched on digitisation, because what we find at the moment is that too many of these processes are manual. So in order to better capture the data, we’re working with a number of equipment manufacturers to automate the process, because once you do that, you’re going to capture the data. And then once you capture the data, we can do a lot more with it.
“In relation to the therapeutic advances, the focus until a number of years ago was on mass volumes of chemicals and biologics to treat mainstream illnesses. Now, we’re looking at taking targeted therapies to solid tumours, which we need to be able to scale.”
David Blakey: “Initially, nucleotides was work in very defined rare disease populations.
“And now, they’re going in both directions. There’s a group setting up to treat just an individual patient who has a specific mutation, developing a supply switching oligo antisense just for that patient. And that’s happening quite a lot, there’s a lot of activity in that space.
“And it’s also going in the other direction as well, you’ve got product like inclisiran which is for lowering of LDL PCS K9 inhibitor. The prediction is, it’s going to going to treat a lot of patients and as a consequence, the manufacturing needs to catch up.
“We’ve seen the consequences of that with a vaccine, so you can get there. I think that’s the positive message, even with complex reagents that actually get a broad patient usage and patient benefit, which is what we’re all out to achieve.”
Jason Foster: “A question from the audience. Technology developments will come at pace, but is there a concern that early adopters of systems will be at a disadvantage for regular updates? And how do developers plan for improvements in the future?”
Keith Muir: “There’s always going to be continuous change. I don’t think there’s going to be one paradigm that beats everything else, I think it’s going to be a combination of factors that come together a combination of methods.”
James Kusunu: “It’s about starting early to explore what the options are, starting with knowing where you want to get to, and starting to seek out potential partners that you think can be with you as part of that journey. And companies like us, we’re looking for people who we want to partner with, because we want to grow together, we want to help the industry grow.”
Jason Foster: “To add to that, I would say, address technology early, be thinking about manufacturing, how does this process scale? How does it get to a lot of patients?
“We’ve got a follow up question: the regulators are key to enabling cost reduction. Do you think they should start asking questions about process economics?”
James Kusunu: “I think the regulator is very open and forward; they want these therapists to come forward. So having early dialogue with the regulators is really important.
“We are still a fairly emerging industry, we’re all still learning and everyone is very cognizant of that fact. So it’s very rare that you’re going to go to a regulator and they turn you away. In fact, there’s many early engagement programmes that are being put forward, to allow people to engage as soon as possible. And that’s important, because you can double down on the work that you’re trying to do and not speak to people for a year or two, and then find that something has changed.”
Jason Foster: “The regulators are very open, as you said, to creating new pathways for innovators to engage. In the UK context, the MHRA is definitely forward thinking in its approach to creating a regulatory framework that enables distributed manufacturing, for example.
“But as developers ourselves, we all need to be thinking about moving the goalposts to say, what does good look like? What good looks like traditionally has been, we get a product to market. That’s sort of success. I would argue that that is no longer success. Success is how many patients have we successfully treated with therapy – that should be our measuring stick.
“To round up, what have we learned over the last 18 months that we can apply to the advanced therapies field? What are the key positives that are applicable to the advanced therapies industry?”
David Blakey: “The messenger RNA technology side of it; it only really started, seven, eight years ago with more defined products, but quickly realised there was a great opportunity in vaccines.
“And also, Moderna did a great job thinking early on about manufacturing, and actually optimisation of the process, that’s one of the reasons they’ve been successful.
“I think the COVID example, messenger RNA has shown that, with complex biologicals, we shouldn’t be too afraid that solutions will come through. So be positive.”
Jason Foster: “One of the key learnings from our perspective at Ori is thinking about supply chains.
“We were seeing key consumables go out of stock for six months, nine months – you can’t run a clinical trial if you can’t get the raw materials you need. So you need to make sure that you have enough stock, enough inventory, your supply chain’s robust, you’ve got business continuity plans, because obviously we can’t afford to let patients down if we’re out there trying or delivering therapies at scale.
“Any other key learnings from COVID?”
Keith Muir: “The number one is it’s impressive to see what can be done when there’s a defined need, when regulators and developers can move at quite a pace.
“And once that’s shown to be possible, that suggests what the new good should look like – should it take 10 years to get a therapy into the clinic?”
Jason Foster: “Great point. It has been accepted that it takes 10 or 12 years to develop a new product or its market, but maybe that’s not the new paradigm.
“We need to think better, faster.”
This feature is a summary of a debate which was part of Advanced Therapies Integrates 2021.
