CRISM Therapeutics Corporation (CRSP) Earnings Call Transcript & Summary

Good afternoon, and welcome to the CRISM Therapeutics Corporation Investor Presentation. [Operator Instructions] 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 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. Those of you who may recall the last update was in September. And clearly, today, it's in the context of seeking additional funding 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 to start with an introduction, just a refresh, at CRISM Therapeutics, we are a drug delivery company working on how we can improve importantly the safety and efficacy of chemotherapy for cancer patients. If I may, just by virtue of an overview, just as a refresh, we call ourselves a platform for drug delivery company. So with-the technology that we have is, which is certainly ChemoSeed, will be available to and accessible to a number of solid tumor indications. What we're doing at the moment is, as I always give you a run-in to the clinical trial plans that we have. But just quickly on the technology itself, is the term ChemoSeed. ChemoSeed was the innovation of our-our Chief Scientist, Professor Chris McConville. He'd been working with -- in the oncology space for some time and realized there was a way we could much improve the treatment of patients. And this is really 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 is confirmed through the grant of our European patents last year. So our lead product is ChemoSeed and it's combined with a chemotherapy drug called irinotecan. Irinotecan 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 because of the seriousness of it, it's the largest cancer killer of children and young adults under the age of 40. Sadly, the standard care remains unchanged since 2005. And for those on the journey we're starting, we come face, there is no standard care. So it's most important that we progress as quickly as we can with this indication. And the -- what was really pleasing is that the clinical trial I've 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 next year. So by way of a quick refresh on the technology, we've -- this is based on ChemoSeed. And on the chart on the right, you'll see the small, yellowish-colored cylinders. Those are the ChemoSeeds and they're racked out in a plate and this is how they'll be sent to the neurosurgeon for implantation. The cartoon just on the left shows the implantation of the seeds and they're sunk into what we refer to as the resection margin. So once the tumor has been removed, there's certainly always going to be a nominal amount of residual tumor which certainly is [ awful ]. It may be some large pieces, it may just be microscopic amounts of tumor. But certainly, it's this section from which a patient will progress and the tumor does return, which is the real challenge. So we -- on the right, you'll see a schematic of how the implantation is done. The pen-shaped instrument you can see there, termed the ventricular catheter, it's a standard piece of equipment that uses in -- during surgery and it's used to move the tissue around for different purposes. And in our case, it will create that space so we can sink the implants in there. And what we're doing is effectively directly treating the margin. The kind of like roadmap 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 spacing the seeds within that 6 millimeter distance between each. And that sizing and the size of the implants that we laid down will make a space to pop the implant in. It's very simple, straightforward. We have a -- the neurosurgeon has a limited amount of time in which to conduct this procedure and this is -- we are estimating on their guidance of about 30 seconds each. The comments on left on the regulatory side, it's very pleasing. We are being seen as a reformulation, so we don't have any medical device regulations to deal with. So this has been a very clean application with support from the MHRA. One piece of news we received recently which was very pleasing is that a reputable group at the University of Edinburgh ran a machine learning AI program to identify suitable drugs for the treatment of glioblastoma. The system which has now been peer reviewed and published screened some 12,000 drugs, chemotherapy drugs. That was -- produced a shortlist of some 3,500 and they finalized a section of 3 drugs which they felt showed the most potential for GBM. And I mean, I'm pretty certain that irinotecan and next of the topline, SM38, is one of those three drugs they identified. So I believe they are excited to see the progress that we make and if -- when we can do a clinical validation of their work. Success in this and a whole lot of other indications are those listed on the left hand side. So, what's happened since we last spoke? Well, the key thing is that the MHRA has approved us for a phase II registration trial. And that was approved back in -- back at -- back in September. It's -- once -- you know, this open-label study, so very importantly that we can have an open dialog 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 then and how the patients are tolerating the treatments and certainly could report an efficacy signal. The last funding round was key. We were able to initiate the manufacturing of the clinical batch of ChemoSeed, and that is underway. And importantly, we have appointed the clinical research organization set up and manage the 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 well, our first patients will be dosed early next year. And the same, the open-label design -- and open-label, just to be clear, this means that we can -- both the patient and the physician know that the patient is getting treated and what treatment they're getting. And what we will look to see, and this is the reason why we've done a small extension on the part one of the trial, but once we've done the dose escalation, which I'll come on to describe, we will be able to report an efficacy signal. This clearly gives us potential for a conditional market authorization, and to be clear on this what it means for us is that will have a commercial product at that point. I think that puts us in a most unique situation in this and not just in the brain tumor space. So why it matters? It's -- we are on a rapid regulation pathway with the MHRA. The program is called ILAP. We have, you may remember, we secured what's called an Innovation Passport, which is the MHRA's endorsement for the rare disease treatments. ILAP is the -- is their approved orphan drug post, post-Brexit. It's the Innovative Licensing Access Pathway. And this brings the potential, this is a framework we're in for an accelerated approval. And you know, we've had very strong and supportive engagement or conversations with the MHRA. What is a rare tumor? Because I've already touched on this and many of you have heard me before, will understand the -- with recurrent glioblastoma there is no standard care. And -- but the support is out there, that we should be able to leverage technology to make good progress here. And it's this ILAP 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 take up, and it's specifically focused on oncology and also on rare disease, and brain tumor is -- it comes under that category. So what it means is that the FDA, there will be early insight and a thorough review of the data and this ties in other jurisdictions, such as Brazil, Canada, Switzerland, Australia, and others to also participate. So what's happening today? Why is this investor so important? I think in cancer treatment today 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 than 1% actually reaches the tumor 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 this, it's important that the side effects, given the toxicity of these drugs, has a major impact on quality of life. And that is something that we hope to address. In an earlier study, the circulating levels of drug were some thousandfold less than you'd expect on an infusion. So we have the reasons to be optimistic here. And other treatments have come and gone and largely it's due to the side effects and the side effects do clearly then require treatment, and that's additional cost to the health service. And that's something that is part of our agenda. So clearly I'm sure this is one of the reasons why this matters clearly, clinically, and the implant is directed and it's this resection margin I touched on which is where the, where, where glioblastoma, where the tumor will [indiscernible]. And then the challenges that other drugs have is that what's called the blood-brain barrier. The brain has a protective mechanism which makes it very difficult for [indiscernible] like the drugs to cross into the brain. And that's the reason why treatment options are severely limited at this point. And we're getting an example on the -- also from the surgeon's perspective from the images earlier. It does make it very easy for the surgeon. The implantation time is important. We've been told that whatever procedure we introduce must take less than 40 minutes. The NHSN's constraints keeps the surgeon, ideally to perform 2 surgeries a day. If we run on for too long, that limits the number of procedures they can tackle. And clearly, that's unacceptable for it to be reduced. So, another reason I think why we've chosen the final point is why we believe this treatment will be important. It's one of the rare times when we actually can start treating a patient immediately post-surgery. Up until now in the standard of care, a patient may wait some 4, even 6 weeks, maybe longer for recovery from the surgery, prior to any treatments which is typically chemo-radiation, that's chemotherapy with drug, temozolomide and radiotherapy. And over those periods of several weeks that tumor, that residual tumor can grow back really very aggressively. So we believe when the tumor beds are at its lowest volume, we stand the best of the best chance for success. Just to quickly reflect something, you may have seen this before, it's on our pre-clinical results. This was done using, what we call 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 ChemoSeed treatments on them. So if you look at the graph on the left, the black line is the placebo with no treatment at all. As you can see that the condition post-surgery that is very, very serious and the mice have a very short survival. The center two lines, the first one is intravenous, both doses of [ irinotecan ] [indiscernible] using and that's -- the improvement there is typical as is temozolomide, the blue lines to the right. Clearly, it does show an improvement but it is more managing the recurrence than treating it. And here you can see the survival line in red, where the mice were treated with the ChemoSeed treatment containing irinotecan. So this was some really, really positive news. This is 148 days, which is the ethical limit. So at that point, we're no longer permitted to continue and the mice treated on the ChemoSeed treatments were euthanized at that point. And this is where we got really confused about the data. The right-hand pair of panels, you'll see this is treated with the standard of care temozolomide and you can see from when the mouse -- the first mouse passed at day 41, you can already see the tumor is recurring. It does put some delay, but all of those mice that died, lived through the tumor. And the red image on the right are the images of the brains doesn't show that effect. If you look to the panel on the left with ChemoSeed, there is no recurrence at any stage. The mouse that we lost early on in the study, the laboratory's technician reported that they felt it never fully recovered from the surgery, which is quite tricky in this indication. The other 4 show no disease progression whatsoever. So that really gives us reasons to be confident. I'm going through these quickly. This is just that we have been -- done some phase I study, this was some years back. What was written in the key message from this, without going all line by line, is that the drug was safe. And so to inject that chemotherapy directly into brain tissue, which is what happened here, they injected over 30 sites in this resection margin once the tumor had been removed. There was no problem associated with it. Typically, in other instances, a drug called carmustine has been used with a vehicle called Gliadel. That causes 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. So this really gives us reasons to be optimistic about what we have here. And I'd say early next year, we'll be looking to make that clear assessment. Just as one final point, this phase I study was about irinotecan and not about ChemoSeed. This is on a formulation which is injected, which was the predecessor to the ChemoSeed technology that we currently utilize. So this is where it's the important part now. So we're now heading into trial next year and the funding round that we've been in now enables this and gets us through the dose escalation. We have an opening dose in part one, we're starting with, as mentioned, with recovered patients. And these are patients who sadly have followed their initial diagnosis, they've had surgery, the tumor has been slightly returned and they're back for further surgery. We'll start with an opening dose, this is going to be measured in seeds. So 10 seeds for the first patient and that is a dose that's within the safe window that we demonstrated in the phase I study. We will then progress very quickly through up to 30 seeds, which will be patient 4, which we believe will be the maximum treatment dose. The doses are so much dictated by the amount of drug and implants given by the size of the resection cavity. So clearly, before when that assessment is made through a patient's brain scan, to remove a larger tumor, we will need more seeds to treat the resection margin. 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 -- this is where we have been made aware that there is a very clear appetite for an early approval here given the unmet need. For these patients, sadly 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, but safety is the key output of part one that leads into part two. And then we will hopefully start treating patients who are newly diagnosed. And study [indiscernible] positive signal in part two is much more -- sorry, part one should be much more effective within part two. And this is market globalization that we're going for. And this will ideally bring us to a commercial product. The milestones, I appreciate this is not a long list. But actually, we're very clear on what we're doing now. And This is -- where we've been very, very pleased with the response we've had and engagement from our investors. People that have put money in the summer, a lot of them have followed. And a number of new people now see that -- are optimistic now the progress we can make if we close off those 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. And it is that once we show that the treatment is safe, well-tolerated, we're then looking for an efficacy signal of the approval. There is a note here, this obviously will be subject to not only just recruitment, but also ongoing funding requirements. I know that's a sensitive one, but at the moment, that is the money that gives to invest to enable this to happen. The trial is mapped out, so we only pay for the patients that we test in 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. The market opportunity, we're excited about it. We've mentioned before, this is -- we estimate some circle GBP 1.7 billion in totality. That's across the kind of base CNS space. For us this is to achieve standard care, certainly should be achievable. The -- it is a rare disease but clearly we need to, we need to give patients genuine hope that we can make a difference here. And once we've shown 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 that. The market size and the costings, we're still work in progress. On here it does note in the subtext that we have a nominal estimated of GBP 13,500 per patient treatments. That was based on a nice value of quality adjusted life here, GBP 20,000. The metric usually now is in the range up to GBP 30,000. For rare diseases it could be as high as GBP 50,000. So the company will make reassessments of the opportunity here. But we are committed -- CRISM is committed that we make this treatment available for all comers. There are many treatments which are 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 funding challenges that we have with our health system. So final slide. The -- so here we are. We're ready. We've been talking about this for -- on the journey along the way. And we are in discussions, as you're aware, that the technology that we use came out of Professor Chris McConville's work at the University of Birmingham. And so we [indiscernible] to the neurosurgical team there, has been a huge support and a mentor for Professor McConville and for the company in how we bring this through. And they worked -- our medical advisor was from Birmingham, Professor Garth Cruickshank, many of you would have heard on my last update in September. And he has very carefully helped craft the structure of the, of the trial which we just described. So it's dose escalation safety and looking for secondary approach in efficacy in Part 1. And a quick move into Part 2 where we want to demonstrate efficacy for the newly diagnosed. And this is going to be the journey that will start. And in a matter of months, we have to give a short time between each patient to -- once we understand that each dose level is safe and effective, we -- sorry, safe and well-tolerated, we can then move to the next dose. And there will be frequent imaging taken on a 4-weekly basis with all that we can very quickly assess the, the impact. Given as I mentioned that the overall survival for patients in -- sadly with this disease is 14.6 months, so we would expect to see and have an understanding of success at an early stage. And it's this open-label design, permits the, not just the interim analysis, but allows that to be reported. And the MHRA have directed us to keep them aware of progress. And it's the sort of approval here, we believe it will very rapidly open up options for other indications. [indiscernible] we'll have some further news in the future once that program is in 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 other 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 other -- any questions that you may have as as directed by the person who accompanied the opening. Thank you very much for your time and for your attention.

[Operator Instructions] Just while the company take a few moments to review those questions submitted today, I'd like to remind you that a recording of this presentation, along with a copy of the slides and the published Q&A can be accessed via Invest Dashboard. Andrew, as you can see, we have received a number of questions throughout today's presentation. If I please ask you to read out the questions and give responses where appropriate to do so, and I'll pick up from you at the end.

Thanks, [indiscernible]. So couple of questions that came in early on. And I do understand that people are expressing their concern [indiscernible] the recent placing in terms of the effect it has on the share price. The direction you see for the last round, we actually have a stake in this. We're aligned with you. The markets are very difficult. The capital markets are very demanding at the moment. There is a reality, and it is the nature of -- we're in that the next expectation is that they receive the shares at a discount. I'm pleased that on this round, we've minimized the discount compared to, compared to the summer round. But, I have to say, I do feel your -- share your pain. If it could be different then, we would certainly never, never, never do so. But we do have certainty now on testing patients. This runway, this GBP 1 million is so important. Clinical trial costs are expensive. We are planned. It's happening. We will be treating patients. 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 the progressing this study. It is now all operational as you're aware. We don't carry these costs directly internally. We've managed these work packages through third parties. Our manufacturing was actioned back in August. The manufacturing partner that we have has twice manufactured batches of the product on a technology transfer when we updated the manufacturing protocol from Professor McConville's laboratory at Birmingham to what we call CDMO, a Contract Development and Manufacturing Organization. These are the people that manufacture the pharmaceutical-grade materials. That ran seamlessly. They since made a second batch, which is under GLP, Good Laboratory Practice, for animal studies. That was successful. So we are confident now on the GMP, which is the Good Manufacturing Practice batch, which is the clinical batch. We would -- we'll at least receive that materials on time. And as you -- into the first quarter of next year, likely February at this, at this point. Clinical trials take time to set up, so that's another reason. So that's in hand at the moment, and we're filing the paperwork at this point. It does take time. It is frustrating, but, the databases and the secure service to collect the patient data and record it and report it, that does take time to set up. So we are looking, I would say, into the second half of the first quarter. 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, full licensing? To be honest, the options are under review at the moment. The U.K. market is manageable in the first instance. We have opened up discussions with a distribution partner who have a launch program for new drugs. The -- given the severity of brain tumor and essentially the treatments will take place in what we effectively refer to as centers of excellence. Centers of excellence for glioma, which is for brain tumor, there's probably around 14, 15 likely those often that have been endorsed by the Tessa Jowell Brain Cancer Mission for [indiscernible] their ability. They need to be treating somewhere around, I think it's about 75% of their patients need to be high-grade glioma, and these will be our target commercial opportunity in the first instance. 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 supply. It is a small and close network -- community of neurosurgeons, so we hope the news will travel fast. We will be looking for them to partner. Quite what form that will take at this point remains to be seen. And now the clinical trials are set up, it's one of our responsibilities now is to map out some more clarity on the commercial model at this point. And again, it's a good question, and thanks for asking. That is the final question I have at the moment. I don't know, I think perhaps, I'll hand back to the Investor Meet Company. Thank you.

Andrew, thank you for answering all those questions [ that came ] from investors. And of course, the company can review all questions submitted today and will publish those responses on the Investor Meet Company platform. Just before redirecting investors to provide you with their feedback, which is particularly important to the company, can I please just ask you for a few closing comments?

I just want to say thanks everybody. Your support has been invaluable. The investment is key and whatever happens, we can take -- it improves the cash runway that we have. The trial is there. It will continue to run at a pace. Once we reach the treatment dose, like just I mentioned earlier 30 seeds, we will be treating patients to generate that registration data as fast as we can recruit. And steps are being taken to support the recruitment process aligned with our contract research organization. So we look to hopefully have early news for you. It will set it done with best efforts going forward. But thank you again for your support and engagement and taking the time to listen to the presentation today. I'm very grateful. Thank you.

Andrew, thank you for updating investors today. Could I please 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.