Crism Therapeutics (LSE:CRTX) — Interim Results

0:00 Good afternoon, and welcome to the CRISM THERAPEUTICS CORPORATION investor presentation. Throughout this recorded meeting, investors will be in listen only mode. Questions are encouraged and could be submitted at any time by the q and a tab situated on the right hand corner of your screen. Just click q and a, type your question, question, press send. The company may not be in a position to answer every question received during the meeting itself. However, the company can review all questions submitted and publish responses where appropriate to do so. Before we begin, we'd like to submit the following poll. I'd now like to hand you over to Andrew Reb, CEO. Good afternoon, sir. So good afternoon. Thank you for taking the time to

0:31 join this call to update you on our half year results for CRISM THERAPEUTICS CORPORATION. It's a privilege to present our progress since our vision to aim earlier this year. For those of you who don't know us, CRISM THERAPEUTICS, we're a drug delivery technology company, and our primary technology is localized treatments through chemotherapy of solid tumors effectively in the cancer indication.

0:58 Following Honesty on AIM, clear priority was to bring on a new board for the for the company. And the my role here going forward is is chief executive of the company. Just to review my background, I'm a career in health care. I started off as a bench scientist many moons ago with GlaxoSmithKline, moved from a bench bench scientist due to commercial with what is now GE Healthcare, and which was really my business took on my work very much on the commercial side and sales, business development and licensing. My first startup was clinical DXS in Manchester, but joined the founders back in 2009, and we successfully exited to I've been involved in really, my focus has been on on starting and building companies in the in the health in the health care space. Commercial, BD licensing, say, has been my my my priority.

1:54 The the brains of science, my colleague is doctor CRISM THERAPEUTICS. He's his his his invention during his his tenure at the University of Birmingham, and he's a highly highly regarded academic in the the field of formulation drug formulation and and and development. Clearly, as a listed business, we require a span of support with non executive directors, and we have a a lot of talent and a very much complementary team. Our Voting Tech Chair is Doctor. Namine Varwala. Namine, and foremost, is a qualified physician. She's also, and importantly for us, a serial life science business leader. She's achieved numerous successful exits and was head of an example of which, she was head of clinical development at BTG International when it was acquired by Boston Scientific for some $4,000,000,000 back in 2019.

2:50 Importantly, the mean's got a great deal of depth in the contract research space and clinical development experience is going to be very valuable to us going forward. I'm also very pleased to welcome Joey Beany. Joey Joey has has a career in the in the financial markets. His core expertise really has been working with and advising high growth companies on their growth ambitions. He's an AIM expert, and, I guess, is kind of leading role. Was really leading Ron Thornton's capital markets team back in the day when it grew to be the largest independent adviser from AIM. So I hope you will understand we have a great level of complementary skills across the team.

3:38 So really just looking at the background to company just briefly. Chris has really majored on drug delivery for the whole of his career, Probably one of the most forms of developments he he's involved in was the with the of the vagina ringing for HIV treatments. And this this concept of local treatment is something he's really, really embraced, and we've talked to apply that treatment in other indications and certainly regarding cancer. Cancer clearly is a challenge for drugs to reach the tissue for the treatment to be effective. And having this advanced experience, first opportunity really is cervical cancer where it's been understood that less than one percent of the therapy actually reaches the cervix. So clearly, there's an opportunity here. And he's really committed himself now to to working with those cancer indications where there's really a significant unmet unmet need.

4:32 And brain and pancreatic are two of the the the keys for him. And what what we have with the technology that he's created, these implants could actually just be be putting the cast treatment directly into the tumor by literally inserting it through our implantable device, which I'll come on to talk about shortly.

4:53 So importantly, our our highlights, the the company, the the our mission to AIM took place at the on the end of end of May. What So we're really talking about here is just one month on the market for our to our interims. The the our listing was the reverse takeover. The above minerals was a cash shell having having sold sold its assets in March of of last year. The company was committed to retain some of the cash back for a future transaction for its shareholders. As was agreed at the time, we've secured some £1,950,000 in cash to enable us to take the QC technology forward. And as of the end of June, we have $1,862,000,000 in bank.

5:41 And this is a key amount of money because we this will take us through now. Given the clinical quality, the clinical data that we have, we have line of sight now with a Phase two clinical trial, which is a registration trial, ideally starting towards the end of next year. If I may just take a moment to reflect because the this is a real challenge for small companies. There's some great technology that's come through the preclinical phase, but crossing through what we affectionate refers to value of death is just trying to take transition those technologies from preclinical into clinical. And cost wise, regulatory costs, manufacturing costs, it's it can can be quite a hurdle. So this actually is remarkable position to be in in terms of what our our funding position.

6:27 Now given that the period we're looking at is just a warm up on the market, I really wanted to spend just a few minutes on what we've been doing post post period end. The one that I think is just so, so important to us on our journey to to go into clinical trials is the innovation passport. We we put a note out to the to the market just a couple of weeks ago to say that the MHRA, which is the medicines health care and product regulatory agency for The UK, has awarded us the innovation passport, which takes us into a program we we nicknamed iLab. This is the innovative licensing access pathway. And effectively, it's the mission really from MHRA in in this is to is to accelerate the time to market and and facilitating access to novel treatments for for patients.

7:21 The reason these programs come about is where there is significant unmet need, including an example we have of brain tumor. There's a low incidence of disease in the population, so not much research or funding go goes to it. But importantly, it has to be assessed on the basis that it will likely provide a benefit to patients, and that's what we successfully achieved. And this is how it opens up onto this pathway going forward. I mentioned cash burn. We have a finite amount cash. It's really important that we ring fence this cash and we remain focused to deliver what we need to do. We're still looking at other sources of funding, and we're pleased that given CRISM's experience in the formulation space that we were we do offer have offered in the past contract development services.

8:10 And Inputech placed a contract with us for some formulation development work back in July, valued around 230,000. For opportunities for grant funding, we we also received a small grant of 25,000 from Spark. Spark is an interesting fund. Spark actually came out of Stanford University in The US and is is wholly focused on supporting small companies, academics, and other health care physicians really in in opportunities where they need funding for unmet clinical need. The the final point, and so it goes back to one, is our cognitive methodology. Chris and his role with the previous professor, Garth Brooksbank at the University of Birmingham, they've had a phase one study taking the drug within TCAM that we use into the brain.

9:00 This is really important in terms of the the looking at the opportunity for local delivery, as we call it. And and that was just published this last month in the well regarded journal, cancers.

9:15 The investment case, we still believe this is, you know, as laid out in in our mission documents. Risk is clearly key in a healthcare opportunity. And so taking Aribitikan, Aribitikan is well known. It's well understood. It's no long one patent. It originally founded and discovered by Pfizer. It's still used in frontline indications such as such as bowel cancer. So that gives readers the the the risk here. We're in discussion on what are the further work we need to do with the MHRA. We ring fenced some 400,000 should any further work needs to be done. Our plan is, though, to make an application to go for clinical trial authorization to start trials at the end of next year.

10:03 Have been through other assessments on our data so far and the scientific advisory board for leading clinical trial at Birmingham Brain Matrix effectively endorse our technology and and strategy. But importantly, the the market opportunity hasn't been that's a bit attractive for other pharma companies. This has worked well for us. We've had an independent health technology health economic report, say, from page consulting. And based on their figures, the high grade glioma, that's grade three and grade four of brain tumor in the markets of The UK, Europe and The US would total some some $1,770,000,000 So this really is our proving ground for the technology before we move into other indications.

10:49 But again, ILAB is key. That gives us that great engagement with The UK regulator. And they're saying this is targeted to Texas into the markets. And then coming on from there, other indications clearly in due course. So let me just reflect briefly on the technology. So we we we term it. It's implantable and biodegradable. So effectively, we we combine the a chemotherapeutic, in this case, with a TCAD, with a polymer. And this is the the seeds are effectively about the size of grain of rice. So you use phase to visualize how these seeds could be could be imparted into the tumor.

11:39 There are development opportunities around it to incorporate different drugs and personalize the treatments. So probably in the first instance, subject to funding, we would probably look into other indications. Clearly, if we can show merit in the high grade glomification, we really have a great opportunity to take this into other areas, prostate, pancreatic, particularly, and that's sort of another area that Chris is passionate about inside the brain, given that, again, we've got a condition where we've not improved the treatment literally for for decades. So so the first of the applicability, you know, we believe is is really important. Just to give you a snapshot of, you know, how this works in practice, this is a a methodology and a protocol we've been guided by the neurosurgeons.

12:26 And I guess one of it, we it's kind of pleasing in its simplicity. So here, at least we're talking about the brain tumor indication. So we try to resection cavity. So grade three and grade four brain tumor, patients go through surgical removal of the tumor and which the the primary reason for that is to reduce the pressure in the brain, which really clearly generates the symptoms. But despite, you know, the brilliance of the neurosurgeons, there will always be a region of the tumor which is inoperable. And sadly, this is the part where the patient where the patient will progress after a period. So the concept that really is quite simple with Guimaceed is that we've got the drug loaded seeds, we literally will pepper through the resection cavity all these seeds inside those regions, which are the were inoperable.

13:15 And on the right, you can see the methodology here using the seeds. The distribution matters that seeds need to be placed a suitable distance apart to allow for the drug diffusion to treat all the tissue deep into that tumor margin. And we've got a biopsy needle. It's a biopsy needle that we would use then to stick the seeds into into into the tumor tissue. A very important, it's a very quick methodology and neurosurgeons are very clear that we can't have any treatment which is going to extend unnecessarily the time that the patients, the surgeons spend in the theatre.

13:55 I may just also reflect on the drug. You know, Kevin, I've talked talked about risk. This is a well understood drug. The benefits of accelerated review through the MHRA, we believe that we could be on the market in as early as 2028. And that's given early indications from the clinical trials unit. We've been looking probably around a two year improvement for the study. The unmet need as a tort is significant. Currently, survival is just fourteen point six months for glioblastoma. So a signal really we should have an early indication on potential success with our treatment. The reason for the support with MHRA is the peer reviewed paper I mentioned for the previous study, the phase one, if the drug was shown to have low toxicity in the brain. It's only one of only two drugs introduced directly into the brain.

14:52 So, clearly, we already have the curve in terms of of the and, you know, favorable discussions so far with with. This issue of toxicity is so important because the systemic issues, side effects of treatments that are given by tablets or by infusion really often are treatment limiting for patients. So this was what we've seen so far as a positive review. The other benefit with the chemotherapy technology is that we have a sustained release of the drug into the tissue. This isn't just a one shot treatment. We from our laboratory data, we will have a release over at least seven days, it could be as much as thirty to forty five days.

15:42 So that continuous and sustained release of the drug through the tissue and our ongoing treatment, we believe is going to be really important. And that's how we believe we're going to have good clinical performance. The part of the data, this goes back from the early work that was involved in when we we got involved with. The the the general data we've got here is is is compelling. So just explain this very, very quickly, along these lines here. The the the black line coming down is the is the the the animals that didn't survive during during during the treatment, and the placebo actually is of no treatment at all. So you can see, sadly, the the the animals die really, really quite quickly given nature of the disease.

16:34 The important one is the the red line. We lost one mouse too through the through the surgical procedure. But, actually, the mice that from that, the the who had the which is the red line chemiseed. There was no recurrence in any of those animals after a hundred and forty eight days. A hundred and forty eight days isn't a a random number. Just to be clear, a hundred and forty eight days was the ethical limits of the study. So all all my all the animals has to be euthanized at that point. And just to put it in perspective, the other two lines here, the yellow and the green. The yellow line is is a ridotecan, our drug of choice. And so the white one is the green line is temozolomide, which is the current standard of care for brain tumor. Now we haven't chosen temozolomide, but the reason it's a standard of care, you can see here, it has improved efficacy over rimidotecan because it does cause blood brain barrier rather more way more effects than raniticam. Raniticam, we believe, is a safe, more effective drug, and that's how we should take it forward. But clearly, he you can see that the the benefits of local delivery compared to systemic and the the the dosing here of irinotecan and temozolomide are through a transfusion.

17:46 And this is the data that, know, what I can say, I feel it's indicative of a potentially transformational form of treatment. And that's really where we're driving our discussions with the regulators based on this on what we have here.

18:04 Importantly, what's it worth? Well, we've done some work. We've had a independent health economic report prepared, and that was done so taking the instance of disease brain and CNS and the the the estimated value of the treatment for patients. We estimate that the market for The UK, Europe and USA in the breakthrough indication is somewhere in the region of £1,700,000,000 Importantly here, figure we've had for the and there's an estimate for The UK treatment cost of £13,400 is important because it's well within the 20,000 Qualitative Life Year estimates that we expect to be authorized by NICE.

18:51 We don't want this to be some astronomically priced treatment, is going to generate further health inequality. So that is very much an important part of our mission here. The other figures, we have just taken an indicative treatment cost of £10,000 per patient, but given the market sizes, the numbers are certainly significant and the opportunity for indications. So just a final summary. We are on track. We're working now on the clinical trial authorization. This we need to get submitted. Our plan is described in the admission document by the end this year. And it is in the high grade glomerular medication for brain tumor.

19:40 And the cash that we've been fortunate enough to get is going to protected to make sure that we do get to that point. The plan is then for to request the commencement of the clinical trial towards the end of towards the end of last year based on our chemistry formulation with vilatiquette. We mentioned the two year trial window, but we will continue. You know, the cash burn is is key. We have minimal overheads. There's just a few staff costs. Everything is is is going to work, get us to where we need to be. We will pick up opportunities. We can still find the relationship with the University of Birmingham, but we still take on contract work through the team. And so it's also like Evotec we will continue to pick up.

20:29 It's a platform. Think we're starting an amazing journey. There's much we can do if we can prove the in our first indication. And clearly, the sooner we can start to commercialize commercial success, it's obviously the fundamental driver of shareholder value. And I'm under no illusions to where my responsibility sits with this. So what we have is it is unique. Our patents are filed, and we think we can use the client technology across different drugs and different indications. We have every reason to be optimistic. The shareholders that we have, we greatly value your commitment to your optimism here as well for us. And I hope you'll continue to support us going forward.

21:18 So thank you very much for taking your time and attention for the slide. And if I may, happy to talk to any questions. Fantastic. Thank you very much indeed for the presentation. As Andrew said, ladies and gentlemen, do please continue to submit your questions just using the Q and A tab just situated on the right hand corner of your screen. But just while Andrew takes a moment to look through those questions I'd like to remind you the recording of the presentation along with a copy of the slides and the published Q and A can be accessed via your investor dashboard. Andrew, as you can see, we've had several questions that have come through today. If you could just click on that Q and A tab just there and where appropriate to do so, read out the question, give you a response, and I'll pick up from you at end. Thank you. That's great. Thanks, Paul. The first question is, can you tell me more about about the innovation password award? What did the application process involve? What does it mean for the company going forward?

22:12 It's Innovation Password is the most significant. It is the the the kind of the the key to to open the door, the gateway for the the our regulatory our regulatory strategy. So what it involves is the in order to to join Innovation Passport, so you can't go on to iLab, the innovation licensing access pathway without Innovation Passport. So that that is your starting point. Three key criteria for innovation passport is the it has to be a life threatening condition with significant unmet unmet clinical need. If it comes under the rare disease, so there's a low incidence of disease in the population. But importantly, it has to be reviewed that it has a bit of potential for patient benefit.

22:58 And on this basis, the application that we make, which is very detailed around the drug, the dose, the administration, the dates that we've generated so far, which I've just shared with you. When it goes to assessments, there's a steering group, which is not just the MHRA. It also includes the health assessment bodies in Wales and also in Scotland. And importantly, our own health technology assessment agency, NICE, are also part of that panel. So even though it's a rare disease and it's important, just by submitting, it's not a given that you'll be able to join this program. To give you an example of my perspective, I think on the Amatra's website now, there's been globally of course, you can speak globally to to to for a regulatory pathway in The UK, and there's been 229 applications so far. But following review, just a 115 have actually been awarded an individual passport.

23:58 So so we we we've we've we've we've taken some pride in the fact that we've got through this part. What does it mean for us? Key aspects I mentioned is the acceleration regulation review is is the fundamental. But what's important to you, we get a continuous engagement with the MHRA. So that's so we have a rolling review with them. So working through and building regulatory datasets, which is is is really, really important. And then really, it's about the conditional getting through. We put data is just the location numbers. We can get an approval. It will be conditional. So there'll be an ongoing monitoring of the the technology going forward, but it does give us this this quick quick access to to to the market. Just one final point.

24:43 I have also dovetails with us something called Project Orbis. Project Orbis is an FDA strategy initiative for for for The US market, but it also embraces other other regulated jurisdictions, for example, Switzerland, Canada, Australia. So that's something that hopefully we'll get some some in some insight to as soon we move forward. How do you so next question. How do you anticipate hemophilia will be priced? How will it try to be justified in the context of limited competition and the unmet need? Philip may have picked up some of that on the health economic data. So the the guidance that well, the the report estimated that with a we can show an improvement in six months of overall survival.

25:34 That was given an estimated value around 13,005 per patient. So that is well within my understanding of NICE NICE approval for for pricing. Clearly, will be assessed on its merits. The nominal figure for one quality adjusted life year, so that's one disease free period of a year, would normally have an estimate of some £20,000 at the moment. It can go as high as 50 for for unmet need. So but we we really are trying to avoid a situation. Chris keeps reminding me that, you know, this this we want a treatment here given the structure of it, but it's available to all comers. So one thing we're very conscious of is we don't want to be exacerbating this situation regarding health and equating quality.

26:27 Next question. Why do we research the brain tumor at the moment? Are not multiple other cancers at the same time? Great question. It really is financial. We've got a financial amount of money, and I think we're gonna do we have to choose one thing and make sure we do it well. And brain tumor is the one that's where we're starting with. The to put it in context, the time the to to run the trials is also much lengthier. So given the the severity of brain tumor, you know, we will hopefully have a signal really quite quite quite quickly. Other indications, let's say, for example, prostate,

27:09 low blood advanced prostate, you'd have to show an improvement in in treatment over because it's largely a watch and wait situation condition. It could it could be a ten year trial. If it's an advanced patient for prostate, it's probably a five year trial. So we're looking to if we can show proof of concept, and then we can then move very, very, very quickly going forward. Thank you for that question. Next one, what advantages do you have using pre approved drugs from a regulation commercialization standpoint? That's a great question. Clearly, every aspect of the treatment is going through assessments. And we've had an early assessment with MHRA. We've had early conversations with them. The fact is with the drug that is out there, it's still being used. It's well understood toxicity.

27:59 As in the FDA has the mantra of do no harm. We need to make sure that this is the drug is understood. And at this point, for us, we've introduced another variable. We have done work with other companies on novel treatments, but I think we can get get a quicker quicker move going forward now with the the treatment that we have. So I think I'll start that question. Future plans, what are our future plans for day to day funding? Current cash reserve will run dry at some point or we're able to address this. Absolutely. You know, our cash is finite. It can get us to where we want to be, where we're committed to being in our first first indication. We're not spending anything outside of that.

28:48 We don't have offices. We're not funding. You know, we'd love to fund what would our R and D basis. That would jeopardize where we are going forward, so we won't be distracted. We will need to to to replace that at at some point in the future. We certainly don't need anything in the short term. When we're working closely with our with our our city advisers, who are also our advisers as well as and our broker. Another question. Why is there no movement to the share price? You see, there was quite a lot of movement, to be honest, to begin with. We did see a decline in the share price to begin with.

29:35 It's not unusual, you know, post submission. The all of those of us who invested through pharmaceuticals, we are locked in. We currently hold somewhere in region of 73 of the company. But I do fully understand that the incumbent shareholders for what was a bit above minerals, they'd their money to be locked up on a to the six month suspension of the stock following their their listing as to a change in situation to be a cash shell. We also need in order for the complexities of the transactions, that's concluded. It actually took a little bit longer. So I think a number of people did did look did look to sell. At the moment, it it's you know, we we're not that well known. I think we need to get our word out working very closely with Buchanan Communications, who are PO agency. They did an amazing job for us now to try and get the word out. People need to know more about us and what we're doing, and now we're really looking to do that. Our share price has ticked up and it's stabilized. It's ticked up again as we're starting to release the new slope. I think it's important, but it's a responsibility to ensure that we do step up in all of those commitments that we've made.

30:47 So that's a thank you for your question, but it is my focus and I'm acutely aware that there's an expectation that we do show progress. In pharma terms, we're clear what's going to be done in the next several months. And what's the most I'd very much look forward to keeping you updated as we move forward. Fantastic. Andrew, thank you very much indeed for answering all those questions that have come through from investors. Of any further questions do come through, you will have the ability to review those. Andrew, I know you gave a few final words there. I don't know if there's anything further to add. If not, I'll redirect the attendees to give you your feedback. That's fine from my side. Thank you all for your interest. That's great. Look. Thank you very much indeed, Andrew, for updating investors today.

31:32 Can I please ask investors not to close the session as you're now automatically be redirected to provide your feedback in order the team can better understand your views and expectations? This may only take a few moments to complete and is greatly valued by the company. On behalf of the management team of CRISM THERAPUITIES CORPORATION, I'd like to thank you for attending today's presentation, and good afternoon to you all.