Crism Therapeutics (LSE:CRTX) — Investor Presentation

0:00 Good afternoon, and welcome to the CRISM THERAPEUTICS CORPORATION investor presentation. Throughout this recorded presentation, investors will be in listen only mode. Questions are encouraged and could be submitted at any time via the q and a tab situated on the right hand corner of your screen. Simply type in your questions and press send. The company may not be in a position to answer every question it receives during the meeting itself. However, the company can review all questions submitted today and publish responses where it's appropriate to do so. Before we begin, I'd like to submit the following poll. I'd now like to hand you over to Andrew Webb, CEO. Good afternoon, sir. Good afternoon. Welcome to today's CRISM THERAPEUTICS CORPORATION. Thank you very much for take taking the time today. My name is Andrew Webb, and the purpose of today's presentation is to update you on the significant progress we've made over recent months.

0:45 Those of you who may recall the present to last update was in September. And clearly, for today, it's in the context of seeking additional funding through from our existing shareholders through a retail offer which was published. This is a follow on from a successful and oversubscribed placing, which the company did earlier in the week. So as far as introduction, just a refresher. CRISM THERAPEUTICS, we are a drug delivery company working on how we can improve, importantly, the safety and efficacy of chemotherapy for for cancer patients. If I may just by virtue of an overview, just as a refresh, we are ourselves a platform drug delivery company.

1:32 So we believe the technology that we have is, which is certainly Quemacy, will be available to and accessible to a number number of solid tumor indications. What we're doing at the moment, as always, to give you a run into the clinical trial plans that we have. But the just quickly on the technology itself, it's termed QuemaSeed. ChemoSEED was the innovation of our chief scientist, professor CRISM THERAPEUTICS CORPORATION. He'd been working with in the oncology space for some time and realized there was a way we could we could much improve the treatment of patients. And this is really the the clinical performance of chemotherapy is really very much what we're about. And I'm pleased to confirm the novelty of the technology, and this was confirmed through the grant of our European patents last year.

2:22 So our lead product is ChemoSEED, and it's combined with a chemotherapy drug called imidotecan. Imidotecan is a well known, well understood drug originally out of the Pfizer portfolio and is currently still used in first line treatments in other indications, including bowel cancer and in second line for brain tumor. And brain tumor is the indication we're starting our journey with. Brain tumor, many people aren't aware just as the seriousness of it. It's it's it's the it's the largest cancer care of children and young adults 40. Certainly, the standard of care remains unchanged since 2005. And for those on the journey we're starting to recover phase, there is no standard of care. So it's most important that we we progress as as quickly as we can with this this indication.

3:13 And the what is really pleasing is that the clinical trial I come on to describe has been approved by the MHRA, and we will we are scheduled to be dosing our first patients in the first quarter of of next year. So by way of a quick refresh on the on on the technology, we've this is it's term quiver seed. And on the trail of light, you'll see the small, small yellow yellowish colored cylinders. Those are the chemo seeds. And they're they're racked out in a plate, and this is how they'll present it to the neurosurgeon for for implantation. The the cartoon just to the low left shows the the implantation of the seeds, and that's sunk into what we refer to as the resection margin.

3:59 So once once the tumor has been removed, there there's certainly always gonna be a nominal amount of residual tumor, which which certainly is is inoffable. It may be sort of large pieces, maybe just through microscopic amounts of tumor. But certainly, it's this section from which a patient will will progress and the tumor does return, which is the real challenge. So we on the right, you'll see a little schematic of how the implantation is done. The pen shaped instrument, you can see that termed a ventricular catheter. It's a standard piece of equipment that uses during neurosurgery, and it's used to move the tissue around for different purposes. And in our case, it will create that space that we can sync the implants in there. And what we're doing is effectively directly treating the margin.

4:50 The kind of like a road map to the right that indicates the spacing. So we need to take account of the diffusion distance of the drug within the tumor margin. And this is done by the by space spacing the seeds within that that six millimeter distance between each. And that ties in with the size of the implants. They've laid down the bigger space, drop the implant in. It's it's simple, straightforward. We have a the newest surgeon has a limited amount of time on which to conduct this procedure, and this is this is a we are estimating on their guidance somewhere around thirty seconds each. The comment to left on the regulatory side, it's very pleasing. We are being seen as a reformulation, so we we don't have any medical device regulations to deal with. So this has been a very clean application support from the MHRA.

5:36 One piece of news we received recently, which was very pleasing, is that a group at the University of Edinburgh ran a machine learning AI program to identify suitable drugs for for the treatment of glioblastoma. The the system, which is now being peer reviewed and published, screened some 12,000 drugs, chemotherapy drugs. That was produced a short list of three and a half thousand, some three and a half thousand, and they they finalized a selection of of three drugs they they felt showed the most potential for GBM. And I mean, please say that rinotecan, active metabolite SM38 is is one of those three drugs identified. So I believe they are excited to see the progress that we make and that if when we could have a clinical validation of of of their work.

6:24 Success in this will open up other indications and those are listed on the on the right on the left hand side. So what's happened since since we last spoke? Well, the the key thing is that the MHRA has approved us for a phase two registration trial, and that that was approved back back back back in back at back in September. It's once an open label study, so very importantly that we can have an open dialogue with the regulator, and we'll be able to keep not just patients, but also shareholders and others up to date on progress when we first dose our patients and how the patients are tolerating the treatments and certainly for us to report an efficacy signal.

7:10 The last planning round was key. We were able to initiate the manufacturing of the clinical batch of chemoside, and that is underway. And importantly, we have appointed the clinical research organization to set up a managed trial. And that work was initiated back in August, and that's underway. And we look forward to reporting as the sites begin to open. So this is really is a pivotal moment for the company. And our first patients will be dosed early next year. The And same in the open label design. An open label, just to be clear, this means that we can both the patient and physician know that the patient is getting treated and what what treatment they're they're getting. What we will look to see, and this is the reason why we've done a small extension on the on the part one of the trial, that once we've done the dose escalation, which I've come on to describe, we will be able to to report an efficacy an efficacy signal.

8:04 This clearly gives us potential for a conditional market authorization. And to be clear on this, what it means for us is that we will have a commercial product at that point. I think that puts us in a most unique situation in this in not just in the brain tumor space. So why why it matters? It's it's it's it's it's we're on a a rapid regulation pathway with with MHRA. The program is called iLAPE. We have you may remember we we secured what's called innovation passport, which is the MHRA's endorsement for the rare disease treatments. ILAB is the is the equivalent of orphan drug post post Brexit. It's the innovation innovative licensing and access pathway. And this brings to the potential this is the framework we're in for an accelerated approval.

9:09 And but the the support is out there that that we should we should be able to to leverage technology to make good progress here. And it's this ILAB program that's so important. What is really exciting is that we are in that framework, we get access to what's termed project Orbis. This is an FDA program and it's to to take up and it's specifically focused on oncology and also on rare disease And brain tumor is it comes under that that that that that category. So what it means is that the the FDA, there will be early insights in the for review of the data, and this ties in other other jurisdictions such as Brazil, Canada, Switzerland, Australia, and others to to also participate.

9:57 So what do we first have you say? Why why is this, you know, so so so important? And in in cancer treatment today, many, many drugs have limited distribution. So what happens is that cancer therapy is given. It tends to be given either as an injection infusion or a tablet. And often in most cases, the less less than one percent actually reaches the tube itself. And some of it actually has very little absorption into the tumor. So we believe by implanting this, the drug contained within an implant directly into the tumor tissue, we get the best chance of a safe and efficacious dose. And with and with this, it's it's important that the, you know, side effects, given the toxicity of these drugs, has a major impact on quality of life, and that is something that we we we hope to address.

10:47 In an earlier study, the circulating levels of drug were some thousand fold less than you'd expect on a infusion. So we have the reasons to be optimistic here. And to, you know, other treatments have come and gone and largely it's due to the side effects. And the side effects do clearly then require treatments, and that's additional cost to the health service. And that's something that we is part of our agenda. So clearly, I'm sure it's it's well understood why this is matters clearly clinically. The implant is directed. And it and it's and this is resection margin I touched on, which is where the where the where the clear blastoma where the tumor will will be will be cut. And then the challenges that other drugs have is that what's called the blood brain barrier.

11:35 The the the brain has a protective mechanism, which makes it very, very difficult for bloods for drugs to cross into the brain. And that's the reason why why treatment options are severely limited at at at this point. We gave the example on the also from the surgeon's perspective from the images earlier. It does make it very easy for the surgeon implantation time is important. We were being told that that whatever procedure we introduced must take less than forty minutes. The NHS on those constraints, the the surgeon needs ideally perform two surgeries a day. If we run on for too long, that that limits the number of procedures they can tackle. And clearly, that's not acceptable for it to be reduced. So another reason I think, well, just a final point is why we believe this treatment will be important. It's one of the rare times when you we actually can start treating a patient immediately post surgery.

12:32 Up until now in standard of care, patient may wait may wait some four, even six weeks, maybe longer for that for recovery from the surgery prior to any treatment, which is typically chemoradiation. That's chemotherapy with the drug tamsolamide and radiotherapy. And over those period of several weeks, that that that tumor that residual tumor can grow back really very aggressively. Aggressively. So we believe when the tumor bed is at its lowest volume, we stand the best the best chance of success. Just to quickly reflect some of you may have seen this before. It's on our preclinical results. This was done using a patient derived xenograft. So this is a human glioblastoma cell line. It's very aggressive. It was it's implanted into a mouse, and we were then using the chemo seed treatments on them. So if you look at the graph on the left, the black line is a placebo with no treatments at all. And as you can see the condition post surgery is very, very serious.

13:33 Mice have a very short survival. Sensitive lines, the first one is intravenous dose of the drug we're using, and that's the improvement there is typical as is temozolomide, the blue line is to the right. Clearly, it does show an improvement, but it is more managing the recurrence than the the the treating it. And here you can see the survival line in red where where where the the mice which were treated with with the chemo seed treatment containing iridotecan. So this was a really, really positive news. This is a hundred and forty eight days, which is the ethical limit. So so that point, we're no longer permitted to to continue and the the mice say they've gone, the chemistry treatments were were they euthanized at that point.

14:20 And this is where we got really confused about about the data. The white tab panels, you'll see this is this is treated with a standard of care, temozolomide. And you can see from the mouth, the first mouth passed at day forty one. You can already see the treat the tumor is is is recurring. It does put some delay, but all of those mice that died died through through the tumor. And the the red image, the right of the the image of the brains does show that effect. If you look to the panel the panel on the left with chemoside, there is no recurrence at any stage. The mouth, the mouth that we lost early on in the study, the the laboratories technician reported that they felt it never fully recovered from the surgery, which matches quite tricky in this indication. The other four showed no disease progression whatsoever.

15:07 So that really gives us reasons to confident. I'm gonna say it's very quickly. This is just that we have been done some phase one one study. This is some years back. What was the the key message from this, without getting me all line by line, is that the drug was safe. And so to inject a chemotherapy drug directly into brain tissue, which is what here, they they inject over thirty sites in this resection margin once the tumor had been removed. There was no there was no no no problem associated with it. Typically, in other other instances, a drug called Carnstein is being used with a with a vehicle called Glidel. That caused this inflammation, swelling, and it impacts wound healing from the surgery. And the patient then becomes susceptible to infection, which is most serious in this situation.

15:54 So this is this really gives us reasons to be optimistic about what we have here. And, yeah, I'd say early next year, we'll we'll be looking to make make that clear assessment. Just as a one final point, this this phase one study was about Aminotecan, not about ChemoC. This was on a formulation which was injected, which was the predecessor to to the ChemoC technology that we we we currently utilize. So this is where the the where it's the the important part now. So we are we're now heading heading into trial next year, and the the funding round that we've been in now enables this and gets us through this this through the dose escalation. We have an opening dose in part one.

16:42 We're starting with, as mentioned, the current patients. And these are patients who sadly have followed their initial diagnosis, they've had surgery, the tumor has been suddenly returned and they're back for further surgery. We will start with an opening dose. This is going be measured in seeds, so ten seeds for the first patient. And that is a dose that's within the safe window that we demonstrated in the Phase one study. We will then progress very quickly through up to thirty seeds, which will at patient four, which we believe will be the maximum treatment dose. The doses are so much dictated by the amount of drug and implants we give them, but the size of the resection cavity. So clearly, before when that assessment's made through a patient's brain scan, when we move a larger tumor, we will need more seeds to treat the resection margin.

17:30 And that's the reason for the variation. But we need to demonstrate that safety at this stage. We will be looking for an efficacy signal and that's this is where we will be made aware that there is a very clear appetite for an early approval here given the need. For these patients, certainly as I mentioned earlier, there is no standard of care. It's very much a decision between the oncologist and neurosurgeon as to what course of action can and will be taken. Success in certain terms of its safety is the key output of part one that leads into part two. And then we will hope to then start treating patients who are newly diagnosed. And any rescue signal in part two, which is much more so part one should be much more effective within part two.

18:24 And this is market authorization that we're going for, and this will ideally bring us through to a commercial product. The milestones, I appreciate it's a lot of obvious, but actually, we're very clear on what we're doing now. This is the where we've been very, very pleased with the response we've had in engagement from our investors, people that put money in the summer, a lot of them have followed. A number of new people now see that are optimistic now the progress we can make as we dose our first patients early into next year. And this is open label study, which gives us a clear and ongoing dialogue with The UK regulator to say that conversations have been very supportive.

19:14 And it is that once we show that the achievement is safe, well tolerated, we're then looking for an efficacy signal of the approval. There is an idea. This obviously will be subject to not just recruitment, but also ongoing funding requirements. I don't know if it's a sensitive one, but at the moment that is the money that gives us to invest to enable this to happen. The trial is mapped out, but we only pay for the patients that we test and the clinical trial centers that we use. Every effort, please, be confident with the Board is we're making to manage that cash flow as best we can. We are seeking actually seeking non dilutive funding in terms of grants and other routes, and I'll clearly make notifications on success as those discussions progress.

20:03 The market opportunity, we're excited about it. We've mentioned before, this is we estimate some circa 1,700,000,000 in totality. That's across the kind of great CNS space. For us, this is to achieve standard of care, certainly should be achievable. It is a rare disease, but clearly, we need to give patients genuine hope that we can make a difference here. And once we show progress in the brain tumor indication, we do believe as indicated by the table here, we can make start and take this out. And as many of you will be aware, we commenced our second program in prostate cancer, which started back in May. We've had some good early progress on our formulation work with with with that.

20:49 The market size and the costings, we're still in a work in progress. On here, it just notes in the subtext that we have a nominal estimated of £1,300,000 per per patient treatment. That was based on a on a nice value of quality and quality adjusted life here, £20,000. The the the metric usually now is in the range up to 30,000. For rare disease, it could be as high as 50. So the the company will will make a reassessment of the opportunity here. But we are CRISM committed that we we make these treatments available for all all comers. Number of new treatments are which are of of good interest, great interest coming forward. Some of them may end up being prohibitively expensive. And CRISM is not in the business of fueling this health inequality that we're currently seeing, given the the funding challenges that we have with our with our health system.

21:42 So final final slide. The so here we are. We're we are ready. We've been talking about this, but on on the journey along the way, and and we're we're in discussions as you know, where the the technology that we use came out of professor CRISM THERAPEUTICS work at the University of Birmingham, and so we remain strong mates in the neurosurgical team there. There's been a a huge support and a mentor for for for for the company in how we how we bring this through. And they worked our medical adviser is from Birmingham, professor Cooke Shank. Many of you would have heard on the on my last update in September. And he has very carefully helped craft the the structure of the of the trial, which is we we just described. So those escalation safety and looking for second gen protein in in efficacy in part one.

22:30 And a and a quick move into into part two, where we ought to demonstrate efficacy for the newly newly diagnosed. And this is the this is going to be the the the journey that that will start. And in a matter of months, we have to give a a short time between each patient to to once we understand that each dose level is safe and effective, we we so it's safe and well tolerated, we can then move to the next dose. And there will be frequent imaging taken on a four weekly basis with all that we can very, very quickly assess the impacts. Given, as I mentioned, that the overall survival for patients and sadly with this disease is fourteen point six months. So we would expect to see and have an understanding of success at an early stage.

23:20 And this is open label design that permits the not just the interim analysis, but allows that to be reported. And the MHRA have directed us to keep keep aware of of progress. And as the, you know, some approval here, we believe it will very rapidly open up options for other indications. Prostate will be able have some further news in the future as that program extends its early stages, but we look forward to keeping you informed along the way. Clearly, the plan is that success of the brain tumor indication really should open up some opportunities. So with that, I'd like to end the formal presentation. Your time is valuable, and thank you for taking the time. I'd like to open for any any any other any questions that you may have as as directed by InvestoMe company at the opening. Thank you very much for your time and for your attention.

24:14 Andrew, thank you very much for your presentation. If I may just bring back up your camera. Ladies and gentlemen, please do continue to submit your questions just by using the q and a tab situated on the right hand corner of your screen. Just while the company take a few moments to review those questions submitted today, I'd like to remind you that recording of this presentation along with a copy of the slides and the published Q and A can be accessed via investor dashboard. Andrew, as you can see, we have received a number of questions throughout today's presentation. Could I please ask you to read out the questions and keep responses where appropriate to do so, and I'll pick up from you at the end. Thanks, Luke. So couple of questions that came in early on, and I do understand that people are expressing their concern. So it's a very disappointing with the recent placing in terms of the the the effect it has on on the on the share price.

25:02 We the direction you've seen for the last round, we we actually have a, you know, a stake in this. We're we're we're aligned with you. The markets are very difficult. The market capital markets are very demanding at the moment. There is a a reality, and this is the nature of the wherein the the the next expectation is that they receive the the shares at a discount. I'm pleased that on this round, we've minimized the discount compared to the sum amount. But I have to say, do feel your share your pain. If it could be different, then we would certainly be do able so. But we do have certainty now on testing patients. This runway, this million pounds is so important. Clinical trial costs are are expensive. We are we are planned. It's happening. We will be treating patients.

25:49 And I do hope that the market responds favorably at that point. Further question, when is the first patient likely to be dosed in January or March? Our timelines, I would say it's more likely to be March at this point. There is no regulatory hurdle in terms of progressing this this study. It is now all operational. As you're aware, we we don't carry these costs directly internally. We've managed the these work packages through third parties. Our manufacturing was was was actioned back in back in August. The manufacturing partner that we have has twice manufactured batch of the product on our technology transfer, and when we published the manufacturing protocol from FESTMORE CONVERSE laboratory in Birmingham to to what's called a CDMO, a contract developed manufacturing organization.

26:42 These have been what manufactured the the pharmaceutical grade materials. That ran seamlessly. They since made a second batch, which is under GOP, called practice for animal studies. That was successful. So we are confident now on the GMP, which is a good manufacturing practice batch, which is the clinical batch. We would we'll have a we'll receive that materials on time. And they're due into the the first quarter of next year, likely likely February at this at this point. Clinical trials take time to set up. So that's for the reason. So that's in hand at the moment, and we're we're filing the paperwork at this point. It does take time. It it is frustrating, but the the the databases and the the secure service to collect the patient data and record it and report it does take time to set up. So we are looking, I'd say, into the second half of the first quarter.

27:34 But please be assured, this is an exciting part of the journey, and we'll look to keep you informed. Next question. What are your long term plans for commercialization, independent launch, co promotional or full licensing? To be honest, the options are under review at the moment. The The UK market is manageable in the first instance. We have opened up discussions with a distribution partner who have a a launch program for for for new drugs. The given the severity of a brain tumor and the the the essentially, the treatments will take place in what we actually refer to as sense of excellence. Sense of excellence for glioma, which is for brain tumor. There's probably around fourteen, fifteen directly that those often have been endorsed by the Tessagel Brain Cancer Mission for their assessment of ability. They need to to be be treating somewhere around I think it's about seventy five percent of patients need to be high grade glioma, and these will be our target commercial opportunity in the first instance.

28:38 A number of these sites will be joining us as part of the trial, so we will have existing relationships on which to continue ongoing ongoing supply. It is a smaller and close network community neurosurgeons, so we hope that news will travel fast. We will be looking for to to partner. Quite what form that will take at this point remains to be seen. And now the clinical trials is set up, It's one of my my responsibilities now is just to map out some more clarity on the commercial model at this point. And and again, it's a good question, and thanks thanks for asking. That is the final question I have at the moment. I don't know. Think perhaps I'll I'll hand back to the investor company. Thank you. Andrew, thank you for answering all those questions you have from investors. And, of course, the company can review all questions submitted today, and we'll publish those responses on the Investor Meet company platform.

29:35 Just before redirecting investors to provide you with their feedback, which I know is particularly important to the company, can I please just ask you for a few closing comments? I just wanna say thanks so many. Your support has been invaluable. You know, the the investment is is key. And whatever happens we we can take, it proves the the cash runway that we have. The trial is there. It will continue to run at a pace. Once we reach the treatment dose, I've decided I mentioned earlier, 30 seats, we will be treating patients to generate that registration data as fast as we can recruit. And steps have been taken to support the recruitment process aligned with our our contract research organization. So we'll we'll look to to hopefully have early news for you. It will certainly done with best best efforts going forward. But thank you again for your support and engagement and taking the time to to listen to the presentation today.

30:30 I'm very grateful. Thank you. Andrew, thanks for updating investors today. Companies ask investors not to close the session as you now be automatically redirected to provide your feedback in order that the management team can better understand your views and expectations. This will only take a few moments to complete, and I'm sure will be greatly valued by the company. On behalf of the management team of CRISM THERAPEUTICS CORPORATION, we'd like to thank you for attending today's presentation, and good afternoon to you all.