Welcome to Farmer Talk Radio. This podcast is focused on sustained release innovations to reduce patient burden from the twenty twenty four pod Partnership Opportunities in Drug Delivery Conference. For more information on the pod conference, editorials, podcasts, or webcasts, please visit Drug desh Delivery dot org. Thank you and enjoy the podcast.
We have a pretty exciting topic to walk through and also a great panel to guide us through that discussion, and that's on sustained release innovations to reduce patient burden. And maybe just to kick off a little bit on sort of why this topic, and I think that really is around what we would call patient centricity conversations we've
had during the past two days. I think that's a topic that has emerged and popped up recurrently, and at least from my perspective, when we talk about patient centricity, that's really about us as pharmaceutical scientists drug delivery scientists,
putting the patient first and actually recognizing the patient. And in that context, you know technologies that provide sustained release, long acting injectables, implantable based systems, these are technologies which definitely strive to put the patient in the center by hopefully elevating the convenience experience for that patient also ultimately hopefully achieving improved compliance and as the title of this panel discussion also alludes to significantly hopefully reducing the burden
that a patient can experience in taking their medication and also ultimately improving the therapeutic outcomes. And I think what will dive into today is different facets of the world of sustained release technologies, looking into you know, considerations around the technology space, but also other elements such as you know, considerations around the payer et cetera. So, without further ado, I think we'll start out with some self introductions of
the panel that is sitting next to me. So, Adam, do you want to kick us off.
Yes, thank you Steven, and thank you for having me as part of this panel. My name is Adam Mendelssohn. I am one of the co founders and the CEO of Vivani Medical. At Vivani Medical, we are aiming to address some of the challenges that Stephen just mentioned with very long acting subdermal drug implants that can provide steady, minimally fluctuating levels of medicine over many months.
At a time.
We're utilizing a novel drug delivery technology that's based on a nanoporus membrane, which is going to be advanced very soon into a first clinical study with a GLP one agonist as our lead program. I've been working in this space drug delivery for many years. In my PhD, I did work with drug delivery and even before that work worked on implantable drug delivery systems for interthecled delivery for
pain management. And it's really a pleasure to be here and participate on this panel with everyone today.
Excellent.
Hi everyone, my name is Manishcripta. This is my first part meeting, enjoying it absolutely. I work at gsk SO I lead the injectable struct product design and development team. I team goes across small molecules and biologics. We add polysorbate to both of those teams. That keeps the interfacial
tension low, keeps us all together. So one of the things that motivates me in terms of patient centricity is the work that we've done in terms of HIV and how we've developed and launched some projects which are long acting injecticles, more small molecules, but a significant trund position from multiple tablets a day to six injections per year, and that makes a huge difference, not just the efficacy, but safety and the patient adherence aspect of brings one
hundred percent compliance when a person actually goes to the doctor and gets their injections.
So very glad to be here today.
Ahi, everyone, My name has been I'm the founder of fast Trax. Fastrax is truct delivery based the CDMO. Over the last twenty years, fastas has developed various microsphere formulations for since their release for our partners. So we leveraged formulation, modify the formulations microsphere formulations to achieve you know, different type of release profiles ranging from like a week to
as many as six months. And you know, we've developed these formulations to different stages preclinical and clinical stage is.
Perfect.
But I think we have an eminent panel and certainly excited to to get the discussion underway. Maybe starting out rather diverting a bit away from technologies from a starting point, but maybe zooming out and considering sort of the bigger picture and ultimately kind of the value proposition that we perceive with you know, sustained release technologies, things that can extend the release of our of our drugs. I think, you know, that's maybe something that intuitively to drug delivery
scientists is very obvious. But you know, we heard, I think quite compelling, an interesting panel discussion earlier this morning from a kind of payers perspective and how they perceive, you know, value proposition of new drug delivery technologies, et cetera. Curious to hear the panel's perspective on, you know, what is the value proposition that we're trying to realize with the types of technologies that each of you are working with.
We'll take a start on that. I think that this is a very important topic because although there are definitely people that would prefer the convenience as being the main reason that they would go with sustained release technologies, there are also very compelling reasons on health outcomes and pharmacoeconomics
why sustained release technologies can be useful. We heard yesterday morning our chair Ali Jackson mentioned one hundred and twenty five thousand patient deaths attributable to non adherence per year, which is more than correctal different breast and breast cancer combined. It's really a tremendous figure. But in addition, to that there are about five hundred billion dollars in avoidable healthcare
costs in the US per year attributable to adherents. There have been studies that have looked at the difference in as an example, clinical trial results where patients are more likely to take their medicine and real world outcomes. One study in the GLP one space a number of years ago showed that a very big delta between clinical trial and real world results that three quarters of that could
be attributed specifically to medication adherents. There have been other studies that have shown in the diabetes field that five hundred dollars per non adherent patient per year can be attributed to non adherence because of hospitalization visits that could have been avoided, acute care visits which could have been avoided.
So having options that all of the people in the ecosystem of a patient's care can feel assured that that patient is getting the medicine that their physician prescribes can have tremendous health outcomes from economic, etc. Advantages, and I think provides real motivation for all of us to do what we can to improve that outcome.
Maybe the other thing I'll add is sometimes it's treatment and it's prevention as well. So if there are aspects of adherence that come into play for patients, they may still take a medicine for treatment, but if it's for prevention, they may not unless some of these options become available, which is a huge factor as well.
Yeah.
Yeah, over the twenty last twenty twenty five years, I think there have been suscetainay release products commune to the market, right, like a lupront depot respital conster, right, and they are about twenty close to twenty sustain release products in the marketplace.
So I think, you know, these these products products proven, have proven their their safety safety, good safety profile, and also they're really helping patients in terms of the compliance right in a use so you don't have to take paills like you know, three times a day, but you can just get it when you know, subke injection every every month or every three months. So so I think
that's really valuable. I think we will continue I see the continuation in that direction developing sustainiy release, but over the you know, again over the last twenty five years, but most efforts have been focused on developing sustained release formulations for small molecules, peptides made to some degree proteins.
But nowadays we are in a nuclear nuclear asset, you know, error, So how do we I think there's a I think the new direction is, uh, at least it's one of the directions is to develop sustainary release formulations for m r n as s r n AS.
I think that's a that's a good segue to maybe the natural next topic. We're mostly scientists or a lot of scientists in the in the audience, and of course also the panel members themselves. You know, from a technology perspective, there are different technology possibilities and domains within sort of
sustained release and also implantable systems. Curious just to hear the panel's perspectives on how they see the technology landscape today and also recognizing that, you know, some of the mainstays of this space, you know, such as PLGA, have been around for actually quite some decades, and maybe there is you know, an opportunity and also a need for introducing you know, new materials and bringing those to the four in terms of realizing you know, potential or possibilities
that we can currently achieve with those formulation concepts that we find in marketed products.
Thoughts.
Maybe I can start so the one that, yeah, you're right. I mean, when you look at the history of say, long acting injectibles, there's all kinds of formulations plg is, microspheres,
We had injectables which were designed in oil vehicles. The ones that comes to mind is just simple long acting injectibles which don't have much in terms of polymers, but they rely on the drug substance itself makes our jobs much easier in terms of unlike oral drug delivery, where you want the solubility of the compound to be really high, you now try to design and optimal solubility such that the release is to keep the concentration below the cmax, avoid the side effects but.
Above the CEMN, which.
Then goes back to design for developability and trying to get the right solubility built.
Into the compound itself.
I think that, combined with the fact that if you can understand the immunogenicity of some of those compounds because the way the deeper forms, there's all kinds of fascinating biology that happens underlying. So I think combining those two into the drug substance itself, you can then design long acting inspectable.
Yeah, I think to bring in the patient centricity aspect to this, I think it will also be important to see how is the patient going to interface with the delivery mechanism for the compound. As an example PLGA who can often require a larger payload and a larger needle gauge. And in the history of GLP ones by Durian, which was the once weekly exenotide, suffered in part by a larger needle gauge. And when Trulicity came on the market, which was the first easy to use version, it quickly,
you know, outpaced the adoption. So I think it's not just the technical considerations that need to be achieved, but also yeah, challenges and how we couple those with delivery technologies that will make it easier for people.
Absolutely, and maybe just an extension maniche of what you were talking about in terms of, of course, you know, we cannot look at these drug delivery technologies in isolation. There's kind of an intimate relationship between the formulation and the drug, and just also maybe people's panel members thoughts reflections in terms of you know what and to what extent we can achieve with you know, innovation on the molecule versus what we can actually do with a formulation
and delivery innovation. I mean, I'm thinking, you know, of course, we have established chemistry principles that can actually extend the half life of you know, many of our compounds for you know, multiple days, maybe up.
To a week.
Do we believe drug delivery technologies can can win the battle of how far you can extend half life or is that something that our friends in chemistry are better or best equipped to achieve.
I think it's a combination absolutely, because I mean people now for oral delivery design molecules to maximize the solubility and simulated intestinal fluid. Now, I think we need to start to look at interstitial fluids for subcutaneous intramuscular delivery and then design the sweet spot in terms of solubility.
And then to your points, see if if you can.
Start to build in vitro and then in silico tools to be able to build these in vitro in vivo relationships and then design the right molecules, then it will become much easier to get to the right drug substance and then the right product.
I think I agree with the manage it it's an atom. It's a combination, right, you know, it's a combination. And there's a device side, there's a formulation side, and there's also you know, different technology modalities where we noticed that
have evolved and also emerging. Right, So like for example, in addition to PHG in micro sladers, there's also you know in situ forming jails, right, you know technology, and ah, there's a also implants, right, there's a so so all these these technologies can provide a different release profile and and uh and so that that's good. But but another thing I want to mention is from the formulation stamp on a side, I noticed the people numerous companies are developing, uh,
synthesizing more new polymers, new barty gradeable materials. They can facilitate, can you know, create like a precise uh you know release profile like very you know, precisely desired to release profile like a reduced further reduced you know burst release and and and and maintain a very yeah flat release release file.
Yeah. I'll just add I think that once the molecule is in systemic circulation, then its circulation half life plays a role in how long it's going to last. But where delivery technologies can play a role is in delaying when that molecule gets into systemic circulation after administration of
the product. So whether that's kind of an intuchu forming gel or an implant, you know, as an example, with our implant, our lead program is delivering a jug with a very very short half life, but the plasma levels are maintained at therapeutic levels because as it gets cleared,
it's continuously being replenished by the device. So as we think about a product profile that's going to be attractive, having a long half life may not be necessary as long as it's coupled with the right delivery technology, But either way can achieve a similar outcome.
Absolutely absolutely.
And maybe another topic that you know, I think many of you were scratching the surface of in some of your comments just a moment ago. That's the kind of the development and the optimization process of you know, whatever drug delivery or drug every system one is developing. In my experience, there still remains a lot to be done in terms of providing a suite of tools that can actually guide the scientists in you know, refining and improving
be it release profile or whatnot. And that's something where we still haven't got as far as I believe we need to in terms of having robust in vitro tools to be predictive of what we can then anticipate to see in vivo curious to hear the perspectives of the of the panel on that and and sort.
Of where where where are we moving and are we moving?
And is it forward?
Yeah.
The one thing that comes to mind, I think is the understanding that we've built with tools like the artificial cut for oral delivery, where we have those tools in the place, and I think that's mostly because we have good mechanistic understanding of what really happens in the human gut.
If we understand what happens upon injection to the implant or the microsphere or the long acting injectable, and I think that kind of an understanding we can build based on imaging studies, So if you can actually image the material, then you can understand what's really going on in terms of release. And that is one of the things that we're working on to build a physiologically based pharmacokinetic model to then predict what the release of the material.
Will be from a depot.
But that I think goes back to the point of cross functional partnerships and collaborations to actually now work with imaging scientists to understand what's really going on.
And in that regard to you, I mean, are there are tools out there and there are publications where people are suggesting and claiming that you know, this is a tool which can predict forecasts. You know what we expect to see in vivo you mentioned Maniche, you know what
is available in the world of oral drug delivery. Is it realistic for us to you know, advance the science in the sub Q space so that we actually can reach a level of you know, predictivity that our colleagues doing oral small molecule drug delivery can can do today?
Or what I think with the cross functional collaboration, I think we can. I hear subcutaneous consortium, I hear the Innovation and Quality Consortium, and how Caesar is being used successfully for the biologics in terms of absorption. So I think, yes, we can get there.
Yeah, excellent, but that's good to be optimistic. Maybe Another consideration, of course, as it relates to long acting or sustained release is of course, when you then do get in vivo, you have to be very patient because these studies are running for typically a very long time, and that I think complicates the drug development process at every stage. Curious to hear the panels sort of thoughts reflections on are there smart ways where we can you know, cut corners?
And by cutting corners, I mean that in a in a in a positive way that we can actually be more efficient in performing conducting in vivo studies. Is that is there a way to do that? Better be good?
So I remember, we we we we created some some systems that where we just uh, you know, we we we we can divide the study, the entire we study into stages right and and and fusted and so we if it's a city day release and then we would this is in virtual if we were started with the
mutual and then we and look at that. We we look at the first you know stage maybe first ten days, and then we see we can see a trend, right and and after many if we do this repeatedly, you know, we create we can kind of predict, right, you know that the system you know what's gonna, what's gonna what's the second phase and the third phase is going to
look like? Right, and and then we can apply this in vivo and and maybe in the first to seven days you can have a very good idea whether your your formination is going to be it's going to work, you know, it's going to give you the profile you need. So that's just the one that approaches we we adapted.
Yeah, I mean, we try to be very strategic with how we intertwine in vitro and in vivo studies to try to get the most useful information as a total as quickly as possible, recognizing the costs of proceeding in each way. And we've definitely found having early in vivo studies to make sure there isn't something very surprising that we're going to find it can be helpful in the development. And we definitely see there are things that in vitro kind of assays or are not predictive of you know.
So it's I hope you're right that we're going to have very predictive in vitro tools that we can use, but for now we can't completely rely on that. So it has to just based on what it is that you're developing, makes good strategic choices as you proceed.
Yeah, the other thing that comes to mind is if it's not in vitrol, can you then translate from pre clinical to clinical? And I think that's another way to look at it is you introduce a few variables into the pre clinical study, then you can start to deconvolute stuff into clinical translation, and then the third variable that you then introduce, you can actually predict what the clinical impact would be.
So that's another way to look at it. If the in vitrol part doesn't work out.
Yeah, so if we if we imagine we succeed in our early pre clinical research and are actually progressing something into the clinic and it's starting to look good, then of course we need to start thinking a bit more deeply on you know, scaling and manufacturing and of course you know the complexity of the formulation or the delivery system can have a profound effect or impact on you know, how scalable and easy it is to manufacture a final
drug product for whatever therapeutic indication one might have in mind. I'm curious just to hear Panels reflection on you know, how we see with current and also emerging opportunities in this technology space, are they can we envisage them to be scalable and how can we achieve that perhaps also with the prospect of you know, treating even more prevalent diseases.
I think today, you know, much of the technologies in this space are are you could say, focused in certain indications, whether it's within the kind of CNS antipsychotic, anti schizophrenia or anti virals as as you mentioned. Also, can we envisage into the future that these technologies being also scale to a level that could treat more prevalent diseases.
I think you can have some benchmarks, right, you know, for example, the existing products they have a certain really profile and certainly establish the manufacturing.
Processes, right.
And then so when approach is that you can use like if it like it really depends on a compound, right it's a very hydrophobic or it's some of them maybe more hydrophilic. Right, So you know, if you you divide you have like an establish some kind of template for like a hydrophobic a compound, then you will see more like a consistency, right. And then for like a very hydrophilic or you know what a soluble compound, then there will be a different type of process processes and
then enough formulation as well. And so based on our experience, and then we found that you know, if we have like a very too similar, like two compounds worth similar hydrophobicity, then they can be you know, the process can be very similar. So I think, yeah, you need to establish a model and and I do understand the complexity complexity of the of the manufacturing for for sucestinari lease formulations.
Yeah.
Yeah.
One of the things that we've painfully found is because there's such an emphasis on speed and acceleration that we ended up using a process which was probably not the most optimal process from a scalability point of view, but it would have gotten us started in a clinical study. But to your point, sometimes it's useful to think through that and design a scalable unit operation such that you can then maintain that acceleration and not hit a pause.
So that's definitely a consideration. Yeah.
My only addition here is that I'm sure it depends on the specific sustained release technology of course, if it leverages existing manufacturing capacities, you know, like for us, you know, there are components that we look for. There is there a supplier that has a scalable process already with the DNF on file as an example, for scalable processes. Those are required before any registration trial would be conducted. Is there any value to data that would be generated principle
proof of principle before that? And how do you organize those efforts in a way that's intelligent. But it depends, and some of them probably are scalable, and many of them we won't know they can get.
No, absolutely, absolutely, I can see where. Just got a couple of minutes left.
So I think maybe a nice way to round off what I think has been otherwise a very engaging discussion. That is, I'm curious to hear each panel members you could say, hopes into the coming years within this space and how you see the space evolving and maybe with some personal perspectives based on you know, your your interests and what you're doing and working in this space. So hopes for the future and where you see things moving.
Yeah, I think again, I just I think the Sustainable Release Formulations is a very good tour, right, you know, it's a very good tour for patient compliance, and it's really benefiting you know, the patients you know that exist in there. Again, twenty twenty products out there, So I hope really you will continue you know, we don't want to, you know, of course we have to develop new our mortalities in new formulations, new technologies. But I think we
can still continue. There's still a lot of compounds that you know out there, I mean compounds drugs there that are off patterns for example, drugs, molecules out there that can be really useful, and I you know, we can hope we can continue to develop you know, those those those proving drug drugs into sustained release formulations.
Yeah, I think we started to have these modified release oral formulations now long acting injectable formulations. To me, I think a little bit of a healthy competition between the industry does a significant benefit. So we keep pushing each other in terms of enhancing that innovation.
Further.
I was quite interested to see how non equis solvents have started to make it into this space, not just for small molecules. I heard quite a few presentations in terms of the biologics as well. So I think just continuing to push boundaries and that healthy competition helps in terms of that next innovation.
So my hope is that all of these molecules which have shown incredible promise in clinical studies, that these delivery technologies, can make them more accessible, can make them have similar real world impacts as what the clinical trials have shown, and thereby addressed that one hundred and twenty five thousand unnecessary patient deaths for five hundred billion dollars in avoidable costs.
And anything that we can do to enable all of these compounds to maximize their potential effects in the real world, I think would be great. We're trying to do that have a body medical but I think there's opportunity across the board with a lot of different technologies to try to have.
That impact absolutely, and I think that's perhaps a really nice way to round off this panel discussion in terms of I think looking into an aspiration that it probably all of us have, in terms of seeing and realizing how drug delivery can be truly enabling and ultimately realizing the desired patient outcomes and as you say, Adam, in the real world and that's where it matters.
Awesome. Thank you.
All panel members for a good discussion, and I think we're all here so if there are questions afterwards, please feel free to drop off to us.
Thank you.
We hope you enjoyed the podcast. For more information about the pod conference, editorials, podcasts, or webcasts, please visit drug delivery dot org. Thanks for listening.