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Clinical Phage Therapy
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Clinical Phage Therapy
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Segment:0 .
JOSHUA JONES: Joshua Jones from Dundee. Josh, I've heard speak a couple of times now and he really does know everything there is to know about phage therapy, and I'm certainly looking forward to his current presentation. Josh, if I could have hand over to you, please.
JOSHUA JONES: Thanks, Rhidian. I don't know everything there is to know about Zoom. I couldn't find the right button, so let me just share my screen. It's an. OK well, thanks very much for inviting me to speak. I'm conscious of time, so I'll try and keep this as short as possible.
JOSHUA JONES: So my name is Josh, I'm a Clinical Phage Specialist and Director of UK Phage Therapy. I've got a general interest in phage therapy for antibiotic refractory infections, but have also supported the treatment of three orthopedic cases here in the UK. So I'm going to assume that lots of you have not heard of phage before. So phages are viruses naturally occurring viruses that infect and kill bacteria.
JOSHUA JONES: They look a bit like this and phages are found wherever bacteria are found. So as we sit here, wherever you are in the world tonight, you are in contact with billions of phages. It is estimated that there are 10 to 31 phages on earth so when we think about those in terms of potential therapeutic agents, that's a mind boggling number and potential combinations. And of course, we've co-evolved with phages over thousands of years.
JOSHUA JONES: So we should keep that in mind when we think about how few side effects or adverse effects we see from phage therapy. So just briefly, the history of phage therapy is really interesting. We won't go into it in detail tonight, but effectively, phage therapy had a golden age in the 1920s and 30s, where it was used quite widely, particularly in the West, but also in the geopolitical East.
JOSHUA JONES: And that was really curtailed by two things; the mass production of antibiotics, but also a lack of knowledge really about what phages were at the time. So this is just to illustrate that phages can be used in two ways. A collection of phages can be used to produce preformulated off the shelf cocktails. And there's a picture here of one that you can buy in pharmacies in Georgia, but also you can use a collection of phages to create personalized phage preps for your patients bacteria.
JOSHUA JONES: So just to summarize some of the advantages perhaps first and most obviously phage of the bacterial killing independent of antibiotic resistance with no notable side effects. And other ones just to highlight tonight are the specificity of phages means they're considered to have minimal impact on commensal flora unlike many of our antibiotics. Particularly relevant for some PJIs, phages have anti-biofilm activity and phages and antibiotics can also synergize by producing or effectively putting two selection pressures, two very different selection pressures onto bacteria.
JOSHUA JONES: And there is clinical and in vitro evidence that of synergy and phage therapy can, in some cases resensitize bugs to antibiotics. And of course, there's the potential for personalized medicine because of the diversity of phages. So we're a bit short on time, but the paper at the top has a good general discussion of the advantages and caveats of phage therapy.
JOSHUA JONES: So moving on to the caveats, actually having a phage that will lyse your or kill your bacteria of interest is not always straightforward and when we've got polymicrobial infections that becomes more challenging. We really want phage for all of them if possible, or at least antibiotic coverage for the rest. And phages do have some drawbacks in the sense that their specificity, while good, obviously creates a very narrow host range and that's overcome by using cocktails of phages.
JOSHUA JONES: Bacteria can and do become resistant to phages and again, the solution there is to fall back on the diversity of phages and switch those phages. And similarly, if we get neutralizing immune responses to phages. Perhaps the key challenge is actually the phage need to come into contact with the bacteria so when you're thinking about this in terms of if you're doing a debridement and you're trying to do a phage wash out in theater, if you miss pockets of infection and you don't get phages where they need to be, then that infection may well come back.
JOSHUA JONES: So just to have a brief look at the evidence for phage therapy. So there is a lot of clinical data, clinical, observational, clinical case data in phage. So there have been around 2,500 cases published across a range of specialties. I've got some efficacy estimates from systematic reviews in the bottom left there, which look reasonably promising. And of course, these are patients largely whose infections were not treatable by antibiotics
JOSHUA JONES: and that body of clinical literature doesn't reveal any notable adverse effects. And there's a nice systematic review here published in 2022 that covers just over 2000 of those cases since the year 2000. And that identified really promising efficacy rates and found that the safety profile of phages was very promising indeed. And where they compared where the clinical trials they included, they compared with control and phage groups, there were more adverse effects or adverse events in the control group.
JOSHUA JONES: So we have this very promising, quite encouraging body of observational data but then we moved to the clinical trials and 13 clinical trials have phaged since the year 2000. I think that's now up to 14 that have been published so I need to update this slide. But all of those encouragingly have shown phages to be safe. However, of the seven trials there that have looked at safety and efficacy, only two of those seven trials have shown evidence of efficacy.
JOSHUA JONES: So we have a, phage therapy suffers from an evidence paradox where the clinical or the observational case data looks fantastic, but the clinical trial data really looks quite poor. And that paradox can be explained because failures simply are not straightforward to you so you need to get enough of the right failures to the right place at the right time. So actually, if we get one bit of that constellation wrong, we won't get efficacy
JOSHUA JONES: and the bottom line is actually, if you read these papers in by their own admission, the five of the seven trials there that haven't shown efficacy have missed one or more of those elements. And again, we're a bit short on time, but if you want a more detailed discussion, there's a paper at the top there. So encouragingly, the American antibiotic resistance leadership group I think a couple of years ago now published considerations for the use of phage therapy and effectively recommended that phage therapy be considered for difficult to treat infections.
JOSHUA JONES: And as we've heard, that's also a growing area of interest in elsewhere in places like Canada. A couple of years later, Health Improvement Scotland, which is the Scottish equivalent of NICE, also carried out its own independent review of phage therapy for antibiotic refractory infections and came to a very similar conclusion. So in terms of interest and a global perspective, we've heard that there's interest in Canada and there is growing global interest in phage therapy and key notable centers in Australia, Europe, Israel,
JOSHUA JONES: the States and it's a real sort of becoming a very hot topic in infection. In terms of the UK, we've been relatively slow to get going on phage therapy, largely because in part because of a lack of our own phage manufacturing so, so all phage cases in the UK at the moment currently rely on imported phages and this is because phages is produced in the UK need to be made in accordance with a manufacturing standard called good manufacturing practice and that's not available in the UK yet.
JOSHUA JONES: And we've also had a long standing misconception that existing medicines regulations in the UK simply don't cater for phages because they're so different. And that's not the case. So at the top you can see a snapshot of MHRA guidance note 14, which sets out the use or governance around the use of unlicensed medicines and phage therapy as any unlicensed medicine in the UK can be considered where licensed alternatives are not meeting a patient's clinical needs
JOSHUA JONES: and that's governed by the MHRA guidance and your local trusts NHS unlicensed medicines policy. So far in the UK we've had two patients receiving lengthy courses of anti mycobacterial phage therapy at Great Ormond Street. And I have overseen the treatment of 10 diabetic foot infection and three orthopedic patients as well
JOSHUA JONES: and that's been across three trusts. And I'm now running UK Phage Therapy, which is currently working with multiple trusts as a not for profit company to continue to make phage therapy available across the UK. So phage therapy has previously been quite difficult to access in the UK. But as I've said, building on my experience of delivering phage therapy across multiple trusts, I'm now providing a National Clinical Phage Service through UK Phage Therapy to streamline that process for all trusts.
JOSHUA JONES: If you are interested in accessing phage therapy for a patient, please do get in touch. Website and email are just here on the slide. So what we do is we support clinicians wanting to use phage therapy at every step from the initial request right through to bedside and we don't charge for this service, but there might be costs involved in acquiring phages from phage suppliers.
JOSHUA JONES: So the time and costs involved will vary depending on the supplier, and that will depend on what your patient has in terms of bacteria. As a broad estimate, it can take anywhere between 2 to 12 months to organize and cost somewhere in the region of 3 to 10,000. pounds but those costs, particularly if you're in the NHS, those costs should be covered by your trust ULN budgets. We can't help you regarding patient selection, but I would strongly recommend looking at the Health Improvement Scotland guidance, which sets out four very broad criteria.
JOSHUA JONES: So antibiotic resistance, antibiotic sensitivity, but clinical recalcitrants which is quite an area of interest in the orthopedic context, high risk of death or significant complications if surgical intervention is used to manage their infection. And a fourth, a sort of weird basket of patient specific factors that preclude the use of conventional antibiotics so allergy intolerance, CKD, that sort of thing. So the sorts of orthopedic requests that we've previously had include patients with effectively biofilms on infected metalwork, deep chronic recalcitrant infections with sinuses or even a few patients with pan resistant organisms.
JOSHUA JONES: And if you do want to discuss a patient, as I said, please do get in touch via the email address here and just include a brief history of pathogens and the science of infection and we can take it from there. Ian, can I just ask in terms of time, do you want me to stop there or are you happy for me to carry on?
IAN KENNEDY: Another couple of minutes maybe just to round up.
JOSHUA JONES: So just a quick very quick look at future challenges.
JOSHUA JONES: So as we saw earlier, we've got this evidence paradox in phage therapy, and that is something that really needs to be resolved. Phage do present challenges to the clinical trial model, particularly around the specificity of phages, the diversity of phages, but also in the complicating factor in some cases that patients will be receiving ongoing antibiotics that might complicate the interpretation of outcomes.
JOSHUA JONES: But it is encouraging to note that there are trials of phage therapy for bone and joint infections ongoing or planned. Belgium, France, the US and Australia. And so I really hope that in a few years time we'll have a substantial body of compelling clinical trial data that will have resolved that present evidence paradox and not just from orthopedics, but there are multiple clinical trials of phage therapy, of course going on for other indications elsewhere as well.
JOSHUA JONES: And it'd be lovely to see a clinical trial in the UK at some point too. Why aren't there any clinical trials in the UK? Well, that's a very good question. And the short answer is that trials in the UK need phages that are produced in accordance with good manufacturing practice. That manufacturing standard we alluded to earlier with GMP and GMP phages are available.
JOSHUA JONES: They can be contract manufactured, but they have been prohibitively expensive without commercial support and that has really been the roadblock to trials here. And as I've said that the biggest barrier really to clinical trials is an almost total lack of private investment and this is particularly acute with naturally occurring phage products.
JOSHUA JONES: In contrast, engineered phage products are much more commercially attracted and are getting investment. For example, engineered phages came fourth in last year's World Economic Forum list of top 10 emerging technologies. So they're up there with things like clean, clean fuel and AI and so on. So they really are getting some attention.
JOSHUA JONES: But I really hope that increased commercial investment will help unblock some of the current challenges around manufacturing. So I'm not going to go through this slide in depth at all, but I just wanted to very briefly summarize some of the research questions, if anything, just to illustrate how much we really don't know. So, for example, there's a really limited knowledge about the best way to use phages and a lot of variety in the way that phages are used in the literature.
JOSHUA JONES: But simple things like dose tissue penetration and to add to the complexity, of course, these parameters might vary between phages. So I think there really are grounds to be optimistic about the potentially transformational impact of phages at all stages of the patient journey and really I hope that what that will translate into is better care for patients, but that'll also translate, I expect, into more savings for the NHS.
JOSHUA JONES: So apologies if I've gone through that rather briskly, but I'll stop there and thank you for your time.
RHIDIAN MORGAN-JONES: Josh, once again, a really clear presentation on what is an emerging field and I'm still staggered that 10,000 pounds per treatment in the scale of PJI management actually isn't that great. Ian, I think we have some questions from the delegates.
IAN KENNEDY: Yes so firstly, Josh, question. How do we deliver phage therapy.
IAN KENNEDY: Is it systemic or local?
JOSHUA JONES: So that will depend on your patient. So the phage therapy is about not just having personalized phage preparations in some respects. So up here we had a patient with staph phage, but also a bespoke Klebsiella phage that had been specifically discovered from Hungarian sewage for this patient. So not just about having a personalized therapy, but also about having a personalized treatment plan.
JOSHUA JONES: And that will depend on the case by case basis. In some cases, local administration, if possible, might be suitable. In other cases, we might want debridement and post-operative administration. In other cases, you might add IV to that. There are in the literature for orthopedic infection, there's a wide range of variation broadly falling into IV within preoperative or intraoperative only.
JOSHUA JONES: That doesn't seem to be any particular difference in terms of which works better and the odd case in the literature will even add an oral phage therapy. So there really is a variety and it does depend on each case has to be looked at on its own merits.
IAN KENNEDY: Good. Next question. Do phages work against fungal infections?
JOSHUA JONES: So unfortunately not, so
JOSHUA JONES: phages are viruses of bacteria unfortunately not, not of fungal organisms.
IAN KENNEDY: OK. Something I think you touched upon in the talk already, but what is the approximate timeline for requesting phage therapy to essentially implementing it?
JOSHUA JONES: Yeah, good question. So the again, it depends on the bug and the complexity of your patients.
JOSHUA JONES: Infection can be as quick as something like two months can be up to something like 12 months. Actually, probably one of the factors that one of the rate limiting steps in there is how fast your own trust will move in terms of moving their unlicensed medicines process along and that varies quite a bit between trusts.
IAN KENNEDY: OK and just the last question, along with the above question, do you believe there is a role in standardization of phage therapy, for example, when, and quantity to allow for better comparison of reported data and ongoing clinical trials.
JOSHUA JONES: So I think at the moment, as I've said, I think we are in a position where we have to this is an unlicensed medicine. We have to treat each case on its own merits, both in terms of therapy and approach. We're a long way from being able to have standardized protocols as we do for antibiotics and the diversity in both in, as we've hinted, in terms of treatment.
JOSHUA JONES: But also in terms of the phage, perhaps that may be used may mean that even when we get to that point, we will still have quite very, very flexible guidelines. But I think in order to get to that point, we need to see much more compelling clinical trial data and we certainly don't have the level of evidence anywhere near the level of evidence that we currently do to be approaching that at the moment. So I think it might be possible eventually to get to a very broad brush sort of guideline around treatment.
JOSHUA JONES: But it's not going to be like antibiotics, I suspect.
IAN KENNEDY: Perfect. So whilst there are some more questions coming through for you, Josh, I think we'll draw things to a close, there. I'm sure people can get in touch with you via the email address you provided for further questions, and I'd like to extend our sincere thanks to all our invited speakers for sharing their expert insights into.
IAN KENNEDY: So Professor Fares Hadad, Dr. Simon Garceau and yourself, Dr. Josh Jones and of course my co-host Rhidian Morgan-Jones for all his hard work behind the scenes with this webinar and BAJIS as a whole. We're grateful to our sponsor for their support and of course, everyone who signed in and actively participated in the discussions. Again, I would encourage you to join BAJIS if you haven't already.
IAN KENNEDY: Membership is free and you can get a lot of valuable resources and updates. Please keep an eye out for us our special session at the BOA annual Congress in September as well. So thanks once again for joining us and enjoy the rest of your evening. Thank you.
Segment:0 .
JOSHUA JONES: Joshua Jones from Dundee. Josh, I've heard speak a couple of times now and he really does know everything there is to know about phage therapy, and I'm certainly looking forward to his current presentation. Josh, if I could have hand over to you, please.
JOSHUA JONES: Thanks, Rhidian. I don't know everything there is to know about Zoom. I couldn't find the right button, so let me just share my screen. It's an. OK well, thanks very much for inviting me to speak. I'm conscious of time, so I'll try and keep this as short as possible.
JOSHUA JONES: So my name is Josh, I'm a Clinical Phage Specialist and Director of UK Phage Therapy. I've got a general interest in phage therapy for antibiotic refractory infections, but have also supported the treatment of three orthopedic cases here in the UK. So I'm going to assume that lots of you have not heard of phage before. So phages are viruses naturally occurring viruses that infect and kill bacteria.
JOSHUA JONES: They look a bit like this and phages are found wherever bacteria are found. So as we sit here, wherever you are in the world tonight, you are in contact with billions of phages. It is estimated that there are 10 to 31 phages on earth so when we think about those in terms of potential therapeutic agents, that's a mind boggling number and potential combinations. And of course, we've co-evolved with phages over thousands of years.
JOSHUA JONES: So we should keep that in mind when we think about how few side effects or adverse effects we see from phage therapy. So just briefly, the history of phage therapy is really interesting. We won't go into it in detail tonight, but effectively, phage therapy had a golden age in the 1920s and 30s, where it was used quite widely, particularly in the West, but also in the geopolitical East.
JOSHUA JONES: And that was really curtailed by two things; the mass production of antibiotics, but also a lack of knowledge really about what phages were at the time. So this is just to illustrate that phages can be used in two ways. A collection of phages can be used to produce preformulated off the shelf cocktails. And there's a picture here of one that you can buy in pharmacies in Georgia, but also you can use a collection of phages to create personalized phage preps for your patients bacteria.
JOSHUA JONES: So just to summarize some of the advantages perhaps first and most obviously phage of the bacterial killing independent of antibiotic resistance with no notable side effects. And other ones just to highlight tonight are the specificity of phages means they're considered to have minimal impact on commensal flora unlike many of our antibiotics. Particularly relevant for some PJIs, phages have anti-biofilm activity and phages and antibiotics can also synergize by producing or effectively putting two selection pressures, two very different selection pressures onto bacteria.
JOSHUA JONES: And there is clinical and in vitro evidence that of synergy and phage therapy can, in some cases resensitize bugs to antibiotics. And of course, there's the potential for personalized medicine because of the diversity of phages. So we're a bit short on time, but the paper at the top has a good general discussion of the advantages and caveats of phage therapy.
JOSHUA JONES: So moving on to the caveats, actually having a phage that will lyse your or kill your bacteria of interest is not always straightforward and when we've got polymicrobial infections that becomes more challenging. We really want phage for all of them if possible, or at least antibiotic coverage for the rest. And phages do have some drawbacks in the sense that their specificity, while good, obviously creates a very narrow host range and that's overcome by using cocktails of phages.
JOSHUA JONES: Bacteria can and do become resistant to phages and again, the solution there is to fall back on the diversity of phages and switch those phages. And similarly, if we get neutralizing immune responses to phages. Perhaps the key challenge is actually the phage need to come into contact with the bacteria so when you're thinking about this in terms of if you're doing a debridement and you're trying to do a phage wash out in theater, if you miss pockets of infection and you don't get phages where they need to be, then that infection may well come back.
JOSHUA JONES: So just to have a brief look at the evidence for phage therapy. So there is a lot of clinical data, clinical, observational, clinical case data in phage. So there have been around 2,500 cases published across a range of specialties. I've got some efficacy estimates from systematic reviews in the bottom left there, which look reasonably promising. And of course, these are patients largely whose infections were not treatable by antibiotics
JOSHUA JONES: and that body of clinical literature doesn't reveal any notable adverse effects. And there's a nice systematic review here published in 2022 that covers just over 2000 of those cases since the year 2000. And that identified really promising efficacy rates and found that the safety profile of phages was very promising indeed. And where they compared where the clinical trials they included, they compared with control and phage groups, there were more adverse effects or adverse events in the control group.
JOSHUA JONES: So we have this very promising, quite encouraging body of observational data but then we moved to the clinical trials and 13 clinical trials have phaged since the year 2000. I think that's now up to 14 that have been published so I need to update this slide. But all of those encouragingly have shown phages to be safe. However, of the seven trials there that have looked at safety and efficacy, only two of those seven trials have shown evidence of efficacy.
JOSHUA JONES: So we have a, phage therapy suffers from an evidence paradox where the clinical or the observational case data looks fantastic, but the clinical trial data really looks quite poor. And that paradox can be explained because failures simply are not straightforward to you so you need to get enough of the right failures to the right place at the right time. So actually, if we get one bit of that constellation wrong, we won't get efficacy
JOSHUA JONES: and the bottom line is actually, if you read these papers in by their own admission, the five of the seven trials there that haven't shown efficacy have missed one or more of those elements. And again, we're a bit short on time, but if you want a more detailed discussion, there's a paper at the top there. So encouragingly, the American antibiotic resistance leadership group I think a couple of years ago now published considerations for the use of phage therapy and effectively recommended that phage therapy be considered for difficult to treat infections.
JOSHUA JONES: And as we've heard, that's also a growing area of interest in elsewhere in places like Canada. A couple of years later, Health Improvement Scotland, which is the Scottish equivalent of NICE, also carried out its own independent review of phage therapy for antibiotic refractory infections and came to a very similar conclusion. So in terms of interest and a global perspective, we've heard that there's interest in Canada and there is growing global interest in phage therapy and key notable centers in Australia, Europe, Israel,
JOSHUA JONES: the States and it's a real sort of becoming a very hot topic in infection. In terms of the UK, we've been relatively slow to get going on phage therapy, largely because in part because of a lack of our own phage manufacturing so, so all phage cases in the UK at the moment currently rely on imported phages and this is because phages is produced in the UK need to be made in accordance with a manufacturing standard called good manufacturing practice and that's not available in the UK yet.
JOSHUA JONES: And we've also had a long standing misconception that existing medicines regulations in the UK simply don't cater for phages because they're so different. And that's not the case. So at the top you can see a snapshot of MHRA guidance note 14, which sets out the use or governance around the use of unlicensed medicines and phage therapy as any unlicensed medicine in the UK can be considered where licensed alternatives are not meeting a patient's clinical needs
JOSHUA JONES: and that's governed by the MHRA guidance and your local trusts NHS unlicensed medicines policy. So far in the UK we've had two patients receiving lengthy courses of anti mycobacterial phage therapy at Great Ormond Street. And I have overseen the treatment of 10 diabetic foot infection and three orthopedic patients as well
JOSHUA JONES: and that's been across three trusts. And I'm now running UK Phage Therapy, which is currently working with multiple trusts as a not for profit company to continue to make phage therapy available across the UK. So phage therapy has previously been quite difficult to access in the UK. But as I've said, building on my experience of delivering phage therapy across multiple trusts, I'm now providing a National Clinical Phage Service through UK Phage Therapy to streamline that process for all trusts.
JOSHUA JONES: If you are interested in accessing phage therapy for a patient, please do get in touch. Website and email are just here on the slide. So what we do is we support clinicians wanting to use phage therapy at every step from the initial request right through to bedside and we don't charge for this service, but there might be costs involved in acquiring phages from phage suppliers.
JOSHUA JONES: So the time and costs involved will vary depending on the supplier, and that will depend on what your patient has in terms of bacteria. As a broad estimate, it can take anywhere between 2 to 12 months to organize and cost somewhere in the region of 3 to 10,000. pounds but those costs, particularly if you're in the NHS, those costs should be covered by your trust ULN budgets. We can't help you regarding patient selection, but I would strongly recommend looking at the Health Improvement Scotland guidance, which sets out four very broad criteria.
JOSHUA JONES: So antibiotic resistance, antibiotic sensitivity, but clinical recalcitrants which is quite an area of interest in the orthopedic context, high risk of death or significant complications if surgical intervention is used to manage their infection. And a fourth, a sort of weird basket of patient specific factors that preclude the use of conventional antibiotics so allergy intolerance, CKD, that sort of thing. So the sorts of orthopedic requests that we've previously had include patients with effectively biofilms on infected metalwork, deep chronic recalcitrant infections with sinuses or even a few patients with pan resistant organisms.
JOSHUA JONES: And if you do want to discuss a patient, as I said, please do get in touch via the email address here and just include a brief history of pathogens and the science of infection and we can take it from there. Ian, can I just ask in terms of time, do you want me to stop there or are you happy for me to carry on?
IAN KENNEDY: Another couple of minutes maybe just to round up.
JOSHUA JONES: So just a quick very quick look at future challenges.
JOSHUA JONES: So as we saw earlier, we've got this evidence paradox in phage therapy, and that is something that really needs to be resolved. Phage do present challenges to the clinical trial model, particularly around the specificity of phages, the diversity of phages, but also in the complicating factor in some cases that patients will be receiving ongoing antibiotics that might complicate the interpretation of outcomes.
JOSHUA JONES: But it is encouraging to note that there are trials of phage therapy for bone and joint infections ongoing or planned. Belgium, France, the US and Australia. And so I really hope that in a few years time we'll have a substantial body of compelling clinical trial data that will have resolved that present evidence paradox and not just from orthopedics, but there are multiple clinical trials of phage therapy, of course going on for other indications elsewhere as well.
JOSHUA JONES: And it'd be lovely to see a clinical trial in the UK at some point too. Why aren't there any clinical trials in the UK? Well, that's a very good question. And the short answer is that trials in the UK need phages that are produced in accordance with good manufacturing practice. That manufacturing standard we alluded to earlier with GMP and GMP phages are available.
JOSHUA JONES: They can be contract manufactured, but they have been prohibitively expensive without commercial support and that has really been the roadblock to trials here. And as I've said that the biggest barrier really to clinical trials is an almost total lack of private investment and this is particularly acute with naturally occurring phage products.
JOSHUA JONES: In contrast, engineered phage products are much more commercially attracted and are getting investment. For example, engineered phages came fourth in last year's World Economic Forum list of top 10 emerging technologies. So they're up there with things like clean, clean fuel and AI and so on. So they really are getting some attention.
JOSHUA JONES: But I really hope that increased commercial investment will help unblock some of the current challenges around manufacturing. So I'm not going to go through this slide in depth at all, but I just wanted to very briefly summarize some of the research questions, if anything, just to illustrate how much we really don't know. So, for example, there's a really limited knowledge about the best way to use phages and a lot of variety in the way that phages are used in the literature.
JOSHUA JONES: But simple things like dose tissue penetration and to add to the complexity, of course, these parameters might vary between phages. So I think there really are grounds to be optimistic about the potentially transformational impact of phages at all stages of the patient journey and really I hope that what that will translate into is better care for patients, but that'll also translate, I expect, into more savings for the NHS.
JOSHUA JONES: So apologies if I've gone through that rather briskly, but I'll stop there and thank you for your time.
RHIDIAN MORGAN-JONES: Josh, once again, a really clear presentation on what is an emerging field and I'm still staggered that 10,000 pounds per treatment in the scale of PJI management actually isn't that great. Ian, I think we have some questions from the delegates.
IAN KENNEDY: Yes so firstly, Josh, question. How do we deliver phage therapy.
IAN KENNEDY: Is it systemic or local?
JOSHUA JONES: So that will depend on your patient. So the phage therapy is about not just having personalized phage preparations in some respects. So up here we had a patient with staph phage, but also a bespoke Klebsiella phage that had been specifically discovered from Hungarian sewage for this patient. So not just about having a personalized therapy, but also about having a personalized treatment plan.
JOSHUA JONES: And that will depend on the case by case basis. In some cases, local administration, if possible, might be suitable. In other cases, we might want debridement and post-operative administration. In other cases, you might add IV to that. There are in the literature for orthopedic infection, there's a wide range of variation broadly falling into IV within preoperative or intraoperative only.
JOSHUA JONES: That doesn't seem to be any particular difference in terms of which works better and the odd case in the literature will even add an oral phage therapy. So there really is a variety and it does depend on each case has to be looked at on its own merits.
IAN KENNEDY: Good. Next question. Do phages work against fungal infections?
JOSHUA JONES: So unfortunately not, so
JOSHUA JONES: phages are viruses of bacteria unfortunately not, not of fungal organisms.
IAN KENNEDY: OK. Something I think you touched upon in the talk already, but what is the approximate timeline for requesting phage therapy to essentially implementing it?
JOSHUA JONES: Yeah, good question. So the again, it depends on the bug and the complexity of your patients.
JOSHUA JONES: Infection can be as quick as something like two months can be up to something like 12 months. Actually, probably one of the factors that one of the rate limiting steps in there is how fast your own trust will move in terms of moving their unlicensed medicines process along and that varies quite a bit between trusts.
IAN KENNEDY: OK and just the last question, along with the above question, do you believe there is a role in standardization of phage therapy, for example, when, and quantity to allow for better comparison of reported data and ongoing clinical trials.
JOSHUA JONES: So I think at the moment, as I've said, I think we are in a position where we have to this is an unlicensed medicine. We have to treat each case on its own merits, both in terms of therapy and approach. We're a long way from being able to have standardized protocols as we do for antibiotics and the diversity in both in, as we've hinted, in terms of treatment.
JOSHUA JONES: But also in terms of the phage, perhaps that may be used may mean that even when we get to that point, we will still have quite very, very flexible guidelines. But I think in order to get to that point, we need to see much more compelling clinical trial data and we certainly don't have the level of evidence anywhere near the level of evidence that we currently do to be approaching that at the moment. So I think it might be possible eventually to get to a very broad brush sort of guideline around treatment.
JOSHUA JONES: But it's not going to be like antibiotics, I suspect.
IAN KENNEDY: Perfect. So whilst there are some more questions coming through for you, Josh, I think we'll draw things to a close, there. I'm sure people can get in touch with you via the email address you provided for further questions, and I'd like to extend our sincere thanks to all our invited speakers for sharing their expert insights into.
IAN KENNEDY: So Professor Fares Hadad, Dr. Simon Garceau and yourself, Dr. Josh Jones and of course my co-host Rhidian Morgan-Jones for all his hard work behind the scenes with this webinar and BAJIS as a whole. We're grateful to our sponsor for their support and of course, everyone who signed in and actively participated in the discussions. Again, I would encourage you to join BAJIS if you haven't already.
IAN KENNEDY: Membership is free and you can get a lot of valuable resources and updates. Please keep an eye out for us our special session at the BOA annual Congress in September as well. So thanks once again for joining us and enjoy the rest of your evening. Thank you.
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